Gastroesophageal Reflux Disease
Conditions
Brief summary
The objectives of this study are to evaluate the safety, efficacy, and dose-response relationship of IW-3718 administered orally to participants who have GERD and continue to experience GERD symptoms while receiving once-daily (QD), standard-dose proton pump inhibitors (PPIs).
Interventions
Sponsors
Ironwood Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
* 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline to Week 8 in Weekly Heartburn Severity Score (WHSS) | Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Week 8 | The WHSS for an analysis week was defined as the average of available DHSS during that week. DHSS was defined as the maximum on a 6-point scale (0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe) of the 3 items measuring heartburn ( Heartburn, Burning feeling behind breastbone or in the center of the upper stomach, and Pain behind breastbone or in the center of the upper stomach,) from a particular day. A negative change from Baseline indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 8 in WHSS | Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Week 8 | The WHSS for an analysis week was defined as the average of available DHSS during that week. DHSS was defined as the maximum on a 6-point scale (0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe) of the 3 items measuring heartburn ( Heartburn, Burning feeling behind breastbone or in the center of the upper stomach, and Pain behind breastbone or in the center of the upper stomach,) from a particular day. A negative change from Baseline indicates improvement. |
| Change From Baseline to Week 4 in WHSS | Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Week 4 | The WHSS for an analysis week was defined as the average of available DHSS during that week. DHSS was defined as the maximum on a 6-point scale (0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe) of the 3 items measuring heartburn ( Heartburn, Burning feeling behind breastbone or in the center of the upper stomach, and Pain behind breastbone or in the center of the upper stomach,) from a particular day. A negative change from Baseline indicates improvement. |
| Percentage of Participants Who Are Overall Heartburn Responders | Week 8 | An overall heartburn responder is a participant who is a weekly heartburn responder for at least 4 of the 8 treatment weeks and for at least 1 of the final 2 treatment weeks (i.e., Week 7 and Week 8). A weekly heartburn responder is a participant with a decrease of \>= 30% from baseline in WHSS (see Outcome Measure 1 for description of WHSS). A participant who reported heartburn severity for less than 4 days during a week was not considered a responder for that week. |
| Percentage of Participants With a DHSS of No More Than Very Mild (≤ 1) on Any Day During Week 8 | Week 8 | DHSS was defined as the maximum on a 6-point scale (0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe) of the 3 items measuring heartburn ( Heartburn, Burning feeling behind breastbone or in the center of the upper stomach, and Pain behind breastbone or in the center of the upper stomach,) from a particular day. A participant who reported heartburn severity for less than 4 days during a week was not considered a responder for that week. |
| Percentage of Participants With a DHSS of No More Than Very Mild (≤ 1) on Any Day During Week 4 | Week 4 | DHSS was defined as the maximum on a 6-point scale (0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe) of the 3 items measuring heartburn ( Heartburn, Burning feeling behind breastbone or in the center of the upper stomach, and Pain behind breastbone or in the center of the upper stomach,) from a particular day. A participant who reported heartburn severity for less than 4 days during a week was not considered a responder for that week. |
| Change From Baseline in the Number of Days Where DHSS Was No More Than Very Mild (≤ 1) During Week 8 | Week 8 | DHSS was defined as the maximum on a 6-point scale (0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe) of the 3 items measuring heartburn ( Heartburn, Burning feeling behind breastbone or in the center of the upper stomach, and Pain behind breastbone or in the center of the upper stomach,) from a particular day. |
| Change From Baseline in the Number of Days Where DHSS Was No More Than Very Mild (≤ 1) During Week 4 | Week 4 | DHSS was defined as the maximum on a 6-point scale (0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe) of the 3 items measuring heartburn ( Heartburn, Burning feeling behind breastbone or in the center of the upper stomach, and Pain behind breastbone or in the center of the upper stomach,) from a particular day. |
| Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Weeks 1, 2, 3, 4, 5, 6, 7, 8 | The mRESQ-eD questionnaire assesses the severity and frequency of the symptoms participants experience due to reflux disease. Participants were asked to rate the severity of their heartburn over the past 24 hours on a 6-point scale: 0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe. Daily scores were averaged each week. A negative change from Baseline indicates improvement. |
| Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Weeks 1, 2, 3, 4, 5, 6, 7, 8 | The mRESQ-eD questionnaire assesses the severity and frequency of the symptoms participants experience due to reflux disease. Participants were asked to rate the severity of their burning feeling behind the breastbone or in the center of the upper stomach over the past 24 hours on a 6-point scale: 0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe. Daily scores were averaged each week. A negative change from baseline indicates improvement. |
| Percent Change From Baseline to Week 4 in WHSS | Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Week 4 | The WHSS for an analysis week was defined as the average of available DHSS during that week. DHSS was defined as the maximum on a 6-point scale (0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe) of the 3 items measuring heartburn ( Heartburn, Burning feeling behind breastbone or in the center of the upper stomach, and Pain behind breastbone or in the center of the upper stomach,) from a particular day. A negative change from Baseline indicates improvement. |
| Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Weeks 1, 2, 3, 4, 5, 6, 7, 8 | The mRESQ-eD questionnaire assesses the severity and frequency of the symptoms participants experience due to reflux disease. Participants were asked to rate the severity of their difficulty swallowing over the past 24 hours on a 6-point scale: 0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe. Daily scores were averaged each week. A negative change from baseline indicates improvement. |
| Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Weeks 1, 2, 3, 4, 5, 6, 7, 8 | The mRESQ-eD questionnaire assesses the severity and frequency of the symptoms participants experience due to reflux disease. Participants were asked to rate the severity of their hoarseness over the past 24 hours on a 6-point scale: 0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe. Daily scores were averaged each week. A negative change from baseline indicates improvement. |
| Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Weeks 1, 2, 3, 4, 5, 6, 7, 8 | The mRESQ-eD questionnaire assesses the severity and frequency of the symptoms participants experience due to reflux disease. Participants were asked to rate the severity of their cough over the past 24 hours on a 6-point scale: 0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe. Daily scores were averaged each week. A negative change from baseline indicates improvement. |
| Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Weeks 1, 2, 3, 4, 5, 6, 7, 8 | The mRESQ-eD questionnaire assesses the severity and frequency of the symptoms participants experience due to reflux disease. Participants were asked to rate the frequency of their regurgitation (liquid or food moving upwards towards the throat or mouth) over the past 24 hours on a 5-point scale: 0=Never, 1= Rarely, 2=Sometimes, 3=Often, 4=Very often. Daily scores were averaged each week. A negative change from baseline indicates improvement. |
| Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Weeks 1, 2, 3, 4, 5, 6, 7, 8 | The mRESQ-eD questionnaire assesses the severity and frequency of the symptoms participants experience due to reflux disease. Participants were asked to rate the frequency of an acid or bitter taste in the mouth over the past 24 hours on a 5-point scale: 0=Never, 1= Rarely, 2=Sometimes, 3=Often, 4=Very often. Daily scores were averaged each week. A negative change from baseline indicates improvement. |
| Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Weeks 1, 2, 3, 4, 5, 6, 7, 8 | The mRESQ-eD questionnaire assesses the severity and frequency of the symptoms participants experience due to reflux disease. Participants were asked to rate the frequency of their cough over the past 24 hours on a 5-point scale: 0=Never, 1= Rarely, 2=Sometimes, 3=Often, 4=Very often. Daily scores were averaged each week. A negative change from baseline indicates improvement. |
| Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Weeks 1, 2, 3, 4, 5, 6, 7, 8 | The mRESQ-eD questionnaire assesses the severity and frequency of the symptoms participants experience due to reflux disease. Participants were asked to rate the frequency of their burping over the past 24 hours on a 5-point scale: 0=Never, 1= Rarely, 2=Sometimes, 3=Often, 4=Very often. Daily scores were averaged each week. A negative change from baseline indicates improvement. |
| Change From Baseline in the Proportion of Heartburn-Free Days During Week 8 | Week 8 | A heartburn free day was a day where DHSS = 0. DHSS was defined as the maximum on a 6-point scale (0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe) of the 3 items measuring heartburn ( Heartburn, Burning feeling behind breastbone or in the center of the upper stomach, and Pain behind breastbone or in the center of the upper stomach,) from a particular day. |
| Change From Baseline in the Proportion of Heartburn-Free Days During Week 4 | Week 4 | A heartburn free day was a day where DHSS = 0. DHSS was defined as the maximum on a 6-point scale (0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe) of the 3 items measuring heartburn ( Heartburn, Burning feeling behind breastbone or in the center of the upper stomach, and Pain behind breastbone or in the center of the upper stomach,) from a particular day. |
| Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Weeks 1, 2, 3, 4, 5, 6, 7, 8 | The mRESQ-eD questionnaire assesses the severity and frequency of the symptoms participants experience due to reflux disease. Participants were asked to rate the severity of their pain behind the breastbone or in the center of the upper stomach over the past 24 hours on a 6-point scale: 0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe. Daily scores were averaged each week. A negative change from baseline indicates improvement. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo BID Matching placebo BID | 70 |
| 500 mg IW-3718 BID 500 mg IW-3718 BID | 71 |
| 1000 mg IW-3718 BID 1000 mg IW-3718 BID | 71 |
| 1500 mg IW-3718 BID 1500 mg IW-3718 BID | 68 |
| Total | 280 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 | 3 | 3 |
| Overall Study | Lost to Follow-up | 1 | 1 | 0 | 1 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 2 | 0 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 3 | 4 | 2 |
Baseline characteristics
| Characteristic | Placebo BID | 500 mg IW-3718 BID | 1000 mg IW-3718 BID | 1500 mg IW-3718 BID | Total |
|---|---|---|---|---|---|
| Age, Continuous | 49.5 years STANDARD_DEVIATION 12.9 | 51.4 years STANDARD_DEVIATION 13.3 | 50.1 years STANDARD_DEVIATION 11.2 | 49.4 years STANDARD_DEVIATION 12.3 | 50.1 years STANDARD_DEVIATION 12.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 23 Participants | 15 Participants | 17 Participants | 64 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 61 Participants | 48 Participants | 56 Participants | 51 Participants | 216 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | 3.08 units on a scale STANDARD_DEVIATION 0.63 | 3.01 units on a scale STANDARD_DEVIATION 0.66 | 3.00 units on a scale STANDARD_DEVIATION 0.64 | 3.08 units on a scale STANDARD_DEVIATION 0.66 | 3.04 units on a scale STANDARD_DEVIATION 0.65 |
| mRESQ-eD Item 'Acid or Bitter Taste Frequency' | 2.09 units on a scale STANDARD_DEVIATION 1.06 | 2.25 units on a scale STANDARD_DEVIATION 0.88 | 2.21 units on a scale STANDARD_DEVIATION 0.98 | 2.19 units on a scale STANDARD_DEVIATION 1.01 | 2.18 units on a scale STANDARD_DEVIATION 0.98 |
| mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | 2.85 units on a scale STANDARD_DEVIATION 0.82 | 2.91 units on a scale STANDARD_DEVIATION 0.82 | 2.77 units on a scale STANDARD_DEVIATION 0.82 | 2.98 units on a scale STANDARD_DEVIATION 0.78 | 2.88 units on a scale STANDARD_DEVIATION 0.81 |
| mRESQ-eD Item 'Burping Frequency' | 2.26 units on a scale STANDARD_DEVIATION 1.04 | 2.21 units on a scale STANDARD_DEVIATION 0.91 | 2.33 units on a scale STANDARD_DEVIATION 0.85 | 2.51 units on a scale STANDARD_DEVIATION 0.9 | 2.33 units on a scale STANDARD_DEVIATION 0.93 |
| mRESQ-eD Item 'Coughing Frequency' | 1.65 units on a scale STANDARD_DEVIATION 1.1 | 1.91 units on a scale STANDARD_DEVIATION 1.06 | 1.96 units on a scale STANDARD_DEVIATION 0.99 | 1.96 units on a scale STANDARD_DEVIATION 1 | 1.87 units on a scale STANDARD_DEVIATION 1.04 |
| mRESQ-eD Item 'Cough Severity' | 1.78 units on a scale STANDARD_DEVIATION 1.27 | 2.11 units on a scale STANDARD_DEVIATION 1.26 | 2.21 units on a scale STANDARD_DEVIATION 1.23 | 2.16 units on a scale STANDARD_DEVIATION 1.22 | 2.07 units on a scale STANDARD_DEVIATION 1.25 |
| mRESQ-eD Item 'Difficulty Swallowing Severity' | 1.71 units on a scale STANDARD_DEVIATION 1.19 | 1.81 units on a scale STANDARD_DEVIATION 1.27 | 2.15 units on a scale STANDARD_DEVIATION 1.27 | 2.05 units on a scale STANDARD_DEVIATION 1.17 | 1.93 units on a scale STANDARD_DEVIATION 1.23 |
| mRESQ-eD Item 'Hoarseness Severity' | 1.75 units on a scale STANDARD_DEVIATION 1.18 | 1.81 units on a scale STANDARD_DEVIATION 1.31 | 2.00 units on a scale STANDARD_DEVIATION 1.35 | 1.81 units on a scale STANDARD_DEVIATION 1.31 | 1.84 units on a scale STANDARD_DEVIATION 1.29 |
| mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | 2.73 units on a scale STANDARD_DEVIATION 0.87 | 2.80 units on a scale STANDARD_DEVIATION 0.89 | 2.57 units on a scale STANDARD_DEVIATION 0.95 | 2.85 units on a scale STANDARD_DEVIATION 0.91 | 2.74 units on a scale STANDARD_DEVIATION 0.91 |
| mRESQ-eD Item 'Regurgitation Frequency' | 2.03 units on a scale STANDARD_DEVIATION 0.99 | 2.29 units on a scale STANDARD_DEVIATION 0.8 | 2.11 units on a scale STANDARD_DEVIATION 0.97 | 2.19 units on a scale STANDARD_DEVIATION 0.88 | 2.15 units on a scale STANDARD_DEVIATION 0.92 |
| Race/Ethnicity, Customized Asian | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 12 Participants | 8 Participants | 9 Participants | 10 Participants | 39 Participants |
| Race/Ethnicity, Customized Caucasian | 54 Participants | 62 Participants | 62 Participants | 54 Participants | 232 Participants |
| Race/Ethnicity, Customized Other, Not Specified | 2 Participants | 1 Participants | 0 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Female | 43 Participants | 46 Participants | 43 Participants | 39 Participants | 171 Participants |
| Sex: Female, Male Male | 27 Participants | 25 Participants | 28 Participants | 29 Participants | 109 Participants |
| Weekly Heartburn Severity Score (WHSS) | 3.18 score on a scale STANDARD_DEVIATION 0.64 | 3.19 score on a scale STANDARD_DEVIATION 0.72 | 3.12 score on a scale STANDARD_DEVIATION 0.64 | 3.19 score on a scale STANDARD_DEVIATION 0.71 | 3.17 score on a scale STANDARD_DEVIATION 0.68 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 70 | 0 / 71 | 0 / 71 | 0 / 68 |
| other Total, other adverse events | 16 / 70 | 17 / 71 | 19 / 71 | 12 / 68 |
| serious Total, serious adverse events | 2 / 70 | 1 / 71 | 1 / 71 | 2 / 68 |
Outcome results
Primary
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
Population: modified Intent-to-Treat Population: all randomized participants who received at least one dose of study treatment with values both at baseline and during the Treatment Period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo BID | Percent Change From Baseline to Week 8 in Weekly Heartburn Severity Score (WHSS) | -46.026 percentage change in score | Standard Error 4.078 |
| 500 mg IW-3718 BID | Percent Change From Baseline to Week 8 in Weekly Heartburn Severity Score (WHSS) | -48.978 percentage change in score | Standard Error 4.019 |
| 1000 mg IW-3718 BID | Percent Change From Baseline to Week 8 in Weekly Heartburn Severity Score (WHSS) | -55.063 percentage change in score | Standard Error 4.024 |
| 1500 mg IW-3718 BID | Percent Change From Baseline to Week 8 in Weekly Heartburn Severity Score (WHSS) | -57.969 percentage change in score | Standard Error 4.108 |
p-value: 0.606595% CI: [-14.222, 8.318]ANCOVA
p-value: 0.11695% CI: [-20.318, 2.245]ANCOVA
p-value: 0.0495% CI: [-23.334, -0.551]ANCOVA
p-value: 0.0225trend test
Secondary
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
Population: modified Intent-to-Treat Population: all randomized participants who received at least one dose of study treatment with values at both baseline and treatment week.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo BID | Change From Baseline in the Number of Days Where DHSS Was No More Than Very Mild (≤ 1) During Week 4 | 2.275 days | Standard Error 0.336 |
| 500 mg IW-3718 BID | Change From Baseline in the Number of Days Where DHSS Was No More Than Very Mild (≤ 1) During Week 4 | 2.294 days | Standard Error 0.322 |
| 1000 mg IW-3718 BID | Change From Baseline in the Number of Days Where DHSS Was No More Than Very Mild (≤ 1) During Week 4 | 2.694 days | Standard Error 0.329 |
| 1500 mg IW-3718 BID | Change From Baseline in the Number of Days Where DHSS Was No More Than Very Mild (≤ 1) During Week 4 | 2.736 days | Standard Error 0.327 |
p-value: 0.327595% CI: [-0.464, 1.385]ANCOVA
p-value: 0.967595% CI: [-0.897, 0.935]ANCOVA
p-value: 0.374195% CI: [-0.507, 1.345]ANCOVA
Secondary
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
Population: modified Intent-to-Treat Population: all randomized participants who received at least one dose of study treatment with values at both baseline and treatment week.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo BID | Change From Baseline in the Number of Days Where DHSS Was No More Than Very Mild (≤ 1) During Week 8 | 2.998 days | Standard Error 0.358 |
| 500 mg IW-3718 BID | Change From Baseline in the Number of Days Where DHSS Was No More Than Very Mild (≤ 1) During Week 8 | 2.700 days | Standard Error 0.347 |
| 1000 mg IW-3718 BID | Change From Baseline in the Number of Days Where DHSS Was No More Than Very Mild (≤ 1) During Week 8 | 3.250 days | Standard Error 0.355 |
| 1500 mg IW-3718 BID | Change From Baseline in the Number of Days Where DHSS Was No More Than Very Mild (≤ 1) During Week 8 | 3.510 days | Standard Error 0.359 |
p-value: 0.550495% CI: [-1.279, 0.683]ANCOVA
p-value: 0.617795% CI: [-0.741, 1.244]ANCOVA
p-value: 0.313895% CI: [-0.488, 1.513]ANCOVA
Secondary
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
Population: modified Intent-to-Treat Population: all randomized participants who received at least one dose of study treatment with values at treatment week.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo BID | Change From Baseline in the Proportion of Heartburn-Free Days During Week 4 | 0.141 proportion of days | Standard Error 0.037 |
| 500 mg IW-3718 BID | Change From Baseline in the Proportion of Heartburn-Free Days During Week 4 | 0.142 proportion of days | Standard Error 0.035 |
| 1000 mg IW-3718 BID | Change From Baseline in the Proportion of Heartburn-Free Days During Week 4 | 0.134 proportion of days | Standard Error 0.036 |
| 1500 mg IW-3718 BID | Change From Baseline in the Proportion of Heartburn-Free Days During Week 4 | 0.241 proportion of days | Standard Error 0.036 |
p-value: 0.996195% CI: [-0.1, 0.101]ANCOVA
p-value: 0.882995% CI: [-0.109, 0.094]ANCOVA
p-value: 0.052795% CI: [-0.001, 0.201]ANCOVA
Secondary
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
Population: modified Intent-to-Treat Population: all randomized participants who received at least one dose of study treatment with values at treatment week.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo BID | Change From Baseline in the Proportion of Heartburn-Free Days During Week 8 | 0.276 proportion of days | Standard Error 0.049 |
| 500 mg IW-3718 BID | Change From Baseline in the Proportion of Heartburn-Free Days During Week 8 | 0.256 proportion of days | Standard Error 0.047 |
| 1000 mg IW-3718 BID | Change From Baseline in the Proportion of Heartburn-Free Days During Week 8 | 0.310 proportion of days | Standard Error 0.049 |
| 1500 mg IW-3718 BID | Change From Baseline in the Proportion of Heartburn-Free Days During Week 8 | 0.347 proportion of days | Standard Error 0.049 |
p-value: 0.768995% CI: [-0.155, 0.115]ANCOVA
p-value: 0.628795% CI: [-0.103, 0.17]ANCOVA
p-value: 0.310695% CI: [-0.066, 0.207]ANCOVA
Secondary
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
Population: modified Intent-to-Treat Population: all randomized participants who received at least one dose of study treatment with values at both baseline and treatment week.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Week 6 | -0.870 units on a scale | Standard Error 0.092 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Week 8 | -0.896 units on a scale | Standard Error 0.094 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Week 3 | -0.691 units on a scale | Standard Error 0.082 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Week 5 | -0.868 units on a scale | Standard Error 0.089 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Week 1 | -0.502 units on a scale | Standard Error 0.069 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Week 2 | -0.738 units on a scale | Standard Error 0.084 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Week 4 | -0.797 units on a scale | Standard Error 0.09 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Week 7 | -0.895 units on a scale | Standard Error 0.094 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Week 4 | -0.847 units on a scale | Standard Error 0.088 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Week 6 | -0.966 units on a scale | Standard Error 0.091 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Week 8 | -0.938 units on a scale | Standard Error 0.093 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Week 2 | -0.640 units on a scale | Standard Error 0.082 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Week 1 | -0.374 units on a scale | Standard Error 0.068 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Week 3 | -0.806 units on a scale | Standard Error 0.081 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Week 7 | -0.912 units on a scale | Standard Error 0.092 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Week 5 | -0.920 units on a scale | Standard Error 0.087 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Week 4 | -0.893 units on a scale | Standard Error 0.088 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Week 5 | -0.929 units on a scale | Standard Error 0.087 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Week 1 | -0.401 units on a scale | Standard Error 0.068 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Week 2 | -0.676 units on a scale | Standard Error 0.082 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Week 3 | -0.842 units on a scale | Standard Error 0.081 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Week 6 | -1.009 units on a scale | Standard Error 0.091 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Week 7 | -0.947 units on a scale | Standard Error 0.092 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Week 8 | -1.072 units on a scale | Standard Error 0.093 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Week 4 | -0.952 units on a scale | Standard Error 0.09 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Week 3 | -0.874 units on a scale | Standard Error 0.083 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Week 8 | -1.163 units on a scale | Standard Error 0.095 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Week 7 | -1.053 units on a scale | Standard Error 0.094 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Week 2 | -0.784 units on a scale | Standard Error 0.084 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Week 5 | -1.024 units on a scale | Standard Error 0.089 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Week 1 | -0.530 units on a scale | Standard Error 0.07 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency' | Week 6 | -1.098 units on a scale | Standard Error 0.093 |
Comparison: Week 2p-value: 0.402295% CI: [-0.133, 0.33]ANCOVA
Comparison: Week 1p-value: 0.190295% CI: [-0.064, 0.319]ANCOVA
Comparison: Week 1p-value: 0.302195% CI: [-0.091, 0.292]ANCOVA
Comparison: Week 1p-value: 0.77595% CI: [-0.221, 0.165]ANCOVA
Comparison: Week 2p-value: 0.597195% CI: [-0.169, 0.293]ANCOVA
Comparison: Week 2p-value: 0.702495% CI: [-0.279, 0.188]ANCOVA
Comparison: Week 3p-value: 0.317395% CI: [-0.342, 0.111]ANCOVA
Comparison: Week 3p-value: 0.190695% CI: [-0.378, 0.076]ANCOVA
Comparison: Week 3p-value: 0.117795% CI: [-0.412, 0.046]ANCOVA
Comparison: Week 4p-value: 0.693695% CI: [-0.297, 0.198]ANCOVA
Comparison: Week 4p-value: 0.446695% CI: [-0.343, 0.152]ANCOVA
Comparison: Week 4p-value: 0.222595% CI: [-0.405, 0.095]ANCOVA
Comparison: Week 5p-value: 0.676495% CI: [-0.297, 0.193]ANCOVA
Comparison: Week 5p-value: 0.624395% CI: [-0.306, 0.184]ANCOVA
Comparison: Week 5p-value: 0.215195% CI: [-0.403, 0.091]ANCOVA
Comparison: Week 6p-value: 0.461195% CI: [-0.351, 0.16]ANCOVA
Comparison: Week 6p-value: 0.284995% CI: [-0.394, 0.116]ANCOVA
Comparison: Week 6p-value: 0.083395% CI: [-0.485, 0.03]ANCOVA
Comparison: Week 7p-value: 0.895595% CI: [-0.277, 0.242]ANCOVA
Comparison: Week 7p-value: 0.691695% CI: [-0.312, 0.207]ANCOVA
Comparison: Week 7p-value: 0.234595% CI: [-0.421, 0.103]ANCOVA
Comparison: Week 8p-value: 0.746695% CI: [-0.304, 0.218]ANCOVA
Comparison: Week 8p-value: 0.184395% CI: [-0.437, 0.084]ANCOVA
Comparison: Week 8p-value: 0.047195% CI: [-0.531, -0.003]ANCOVA
Secondary
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
Population: modified Intent-to-Treat Population: all randomized participants who received at least one dose of study treatment with values at both baseline and treatment week.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Week 1 | -0.459 units on a scale | Standard Error 0.071 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Week 2 | -0.669 units on a scale | Standard Error 0.083 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Week 3 | -0.605 units on a scale | Standard Error 0.085 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Week 4 | -0.701 units on a scale | Standard Error 0.092 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Week 5 | -0.744 units on a scale | Standard Error 0.091 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Week 6 | -0.801 units on a scale | Standard Error 0.094 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Week 7 | -0.810 units on a scale | Standard Error 0.099 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Week 8 | -0.809 units on a scale | Standard Error 0.102 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Week 6 | -0.845 units on a scale | Standard Error 0.093 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Week 5 | -0.832 units on a scale | Standard Error 0.09 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Week 2 | -0.649 units on a scale | Standard Error 0.082 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Week 8 | -0.973 units on a scale | Standard Error 0.101 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Week 7 | -0.896 units on a scale | Standard Error 0.098 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Week 4 | -0.794 units on a scale | Standard Error 0.091 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Week 3 | -0.705 units on a scale | Standard Error 0.084 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Week 1 | -0.416 units on a scale | Standard Error 0.07 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Week 7 | -0.803 units on a scale | Standard Error 0.097 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Week 3 | -0.734 units on a scale | Standard Error 0.084 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Week 4 | -0.797 units on a scale | Standard Error 0.09 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Week 5 | -0.813 units on a scale | Standard Error 0.09 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Week 6 | -0.845 units on a scale | Standard Error 0.093 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Week 8 | -0.920 units on a scale | Standard Error 0.1 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Week 1 | -0.309 units on a scale | Standard Error 0.07 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Week 2 | -0.556 units on a scale | Standard Error 0.082 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Week 3 | -0.754 units on a scale | Standard Error 0.086 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Week 4 | -0.866 units on a scale | Standard Error 0.093 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Week 2 | -0.614 units on a scale | Standard Error 0.084 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Week 1 | -0.416 units on a scale | Standard Error 0.071 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Week 5 | -0.910 units on a scale | Standard Error 0.092 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Week 8 | -1.008 units on a scale | Standard Error 0.103 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Week 7 | -0.909 units on a scale | Standard Error 0.1 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency' | Week 6 | -0.942 units on a scale | Standard Error 0.095 |
Comparison: Week 1p-value: 0.665395% CI: [-0.152, 0.238]ANCOVA
Comparison: Week 1p-value: 0.132795% CI: [-0.046, 0.345]ANCOVA
Comparison: Week 1p-value: 0.669795% CI: [-0.155, 0.241]ANCOVA
Comparison: Week 2p-value: 0.859895% CI: [-0.21, 0.251]ANCOVA
Comparison: Week 2p-value: 0.335495% CI: [-0.118, 0.344]ANCOVA
Comparison: Week 2p-value: 0.642995% CI: [-0.179, 0.289]ANCOVA
Comparison: Week 3p-value: 0.40195% CI: [-0.336, 0.135]ANCOVA
Comparison: Week 3p-value: 0.282195% CI: [-0.364, 0.106]ANCOVA
Comparison: Week 3p-value: 0.218995% CI: [-0.388, 0.089]ANCOVA
Comparison: Week 4p-value: 0.471795% CI: [-0.346, 0.161]ANCOVA
Comparison: Week 4p-value: 0.457295% CI: [-0.349, 0.158]ANCOVA
Comparison: Week 4p-value: 0.206495% CI: [-0.422, 0.092]ANCOVA
Comparison: Week 5p-value: 0.493295% CI: [-0.339, 0.164]ANCOVA
Comparison: Week 5p-value: 0.589795% CI: [-0.321, 0.183]ANCOVA
Comparison: Week 5p-value: 0.201495% CI: [-0.421, 0.089]ANCOVA
Comparison: Week 6p-value: 0.738495% CI: [-0.304, 0.215]ANCOVA
Comparison: Week 6p-value: 0.742395% CI: [-0.303, 0.216]ANCOVA
Comparison: Week 6p-value: 0.292395% CI: [-0.404, 0.122]ANCOVA
Comparison: Week 7p-value: 0.538895% CI: [-0.359, 0.188]ANCOVA
Comparison: Week 7p-value: 0.956595% CI: [-0.266, 0.281]ANCOVA
Comparison: Week 7p-value: 0.484895% CI: [-0.376, 0.179]ANCOVA
Comparison: Week 8p-value: 0.252395% CI: [-0.445, 0.117]ANCOVA
Comparison: Week 8p-value: 0.435695% CI: [-0.393, 0.17]ANCOVA
Comparison: Week 8p-value: 0.170695% CI: [-0.485, 0.086]ANCOVA
Secondary
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
Population: modified Intent-to-Treat Population: all randomized participants who received at least one dose of study treatment with values at both baseline and treatment week.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Week 1 | -0.374 units on a scale | Standard Error 0.064 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Week 2 | -0.572 units on a scale | Standard Error 0.081 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Week 3 | -0.477 units on a scale | Standard Error 0.083 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Week 4 | -0.497 units on a scale | Standard Error 0.089 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Week 5 | -0.506 units on a scale | Standard Error 0.095 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Week 6 | -0.594 units on a scale | Standard Error 0.092 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Week 7 | -0.561 units on a scale | Standard Error 0.097 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Week 8 | -0.554 units on a scale | Standard Error 0.095 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Week 6 | -0.653 units on a scale | Standard Error 0.09 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Week 5 | -0.659 units on a scale | Standard Error 0.093 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Week 2 | -0.469 units on a scale | Standard Error 0.079 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Week 8 | -0.647 units on a scale | Standard Error 0.093 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Week 7 | -0.656 units on a scale | Standard Error 0.095 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Week 4 | -0.667 units on a scale | Standard Error 0.087 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Week 3 | -0.605 units on a scale | Standard Error 0.081 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Week 1 | -0.286 units on a scale | Standard Error 0.063 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Week 7 | -0.713 units on a scale | Standard Error 0.095 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Week 3 | -0.594 units on a scale | Standard Error 0.081 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Week 4 | -0.685 units on a scale | Standard Error 0.087 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Week 5 | -0.648 units on a scale | Standard Error 0.093 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Week 6 | -0.700 units on a scale | Standard Error 0.09 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Week 8 | -0.718 units on a scale | Standard Error 0.093 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Week 1 | -0.290 units on a scale | Standard Error 0.063 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Week 2 | -0.484 units on a scale | Standard Error 0.079 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Week 3 | -0.729 units on a scale | Standard Error 0.083 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Week 4 | -0.793 units on a scale | Standard Error 0.089 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Week 2 | -0.571 units on a scale | Standard Error 0.081 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Week 1 | -0.352 units on a scale | Standard Error 0.064 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Week 5 | -0.812 units on a scale | Standard Error 0.095 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Week 8 | -0.988 units on a scale | Standard Error 0.095 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Week 7 | -0.872 units on a scale | Standard Error 0.097 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency' | Week 6 | -0.872 units on a scale | Standard Error 0.092 |
Comparison: Week 1p-value: 0.325895% CI: [-0.088, 0.265]ANCOVA
Comparison: Week 1p-value: 0.348395% CI: [-0.092, 0.261]ANCOVA
Comparison: Week 1p-value: 0.805595% CI: [-0.156, 0.201]ANCOVA
Comparison: Week 2p-value: 0.362795% CI: [-0.119, 0.326]ANCOVA
Comparison: Week 2p-value: 0.440495% CI: [-0.135, 0.31]ANCOVA
Comparison: Week 2p-value: 0.993995% CI: [-0.224, 0.226]ANCOVA
Comparison: Week 3p-value: 0.271695% CI: [-0.356, 0.1]ANCOVA
Comparison: Week 3p-value: 0.317595% CI: [-0.345, 0.112]ANCOVA
Comparison: Week 3p-value: 0.032595% CI: [-0.483, -0.021]ANCOVA
Comparison: Week 4p-value: 0.176995% CI: [-0.415, 0.077]ANCOVA
Comparison: Week 4p-value: 0.134395% CI: [-0.434, 0.058]ANCOVA
Comparison: Week 4p-value: 0.020395% CI: [-0.544, -0.046]ANCOVA
Comparison: Week 5p-value: 0.254395% CI: [-0.415, 0.11]ANCOVA
Comparison: Week 5p-value: 0.289295% CI: [-0.405, 0.121]ANCOVA
Comparison: Week 5p-value: 0.024395% CI: [-0.571, -0.04]ANCOVA
Comparison: Week 6p-value: 0.647195% CI: [-0.312, 0.194]ANCOVA
Comparison: Week 6p-value: 0.412395% CI: [-0.359, 0.148]ANCOVA
Comparison: Week 6p-value: 0.033895% CI: [-0.534, -0.021]ANCOVA
Comparison: Week 7p-value: 0.484195% CI: [-0.362, 0.172]ANCOVA
Comparison: Week 7p-value: 0.262795% CI: [-0.419, 0.115]ANCOVA
Comparison: Week 7p-value: 0.024195% CI: [-0.581, -0.041]ANCOVA
Comparison: Week 8p-value: 0.488195% CI: [-0.355, 0.17]ANCOVA
Comparison: Week 8p-value: 0.220595% CI: [-0.427, 0.099]ANCOVA
Comparison: Week 8p-value: 0.001595% CI: [-0.699, -0.168]ANCOVA
Secondary
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
Population: modified Intent-to-Treat Population: all randomized participants who received at least one dose of study treatment with values at both baseline and treatment week.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Week 1 | -0.426 units on a scale | Standard Error 0.078 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Week 5 | -0.616 units on a scale | Standard Error 0.106 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Week 2 | -0.574 units on a scale | Standard Error 0.095 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Week 6 | -0.634 units on a scale | Standard Error 0.107 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Week 7 | -0.594 units on a scale | Standard Error 0.112 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Week 3 | -0.534 units on a scale | Standard Error 0.092 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Week 8 | -0.613 units on a scale | Standard Error 0.107 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Week 4 | -0.530 units on a scale | Standard Error 0.099 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Week 4 | -0.657 units on a scale | Standard Error 0.097 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Week 8 | -0.706 units on a scale | Standard Error 0.105 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Week 5 | -0.692 units on a scale | Standard Error 0.104 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Week 7 | -0.688 units on a scale | Standard Error 0.11 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Week 3 | -0.614 units on a scale | Standard Error 0.09 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Week 2 | -0.501 units on a scale | Standard Error 0.093 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Week 6 | -0.671 units on a scale | Standard Error 0.105 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Week 1 | -0.283 units on a scale | Standard Error 0.076 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Week 6 | -0.953 units on a scale | Standard Error 0.105 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Week 7 | -0.971 units on a scale | Standard Error 0.11 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Week 8 | -0.949 units on a scale | Standard Error 0.105 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Week 2 | -0.608 units on a scale | Standard Error 0.093 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Week 3 | -0.745 units on a scale | Standard Error 0.09 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Week 1 | -0.353 units on a scale | Standard Error 0.076 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Week 4 | -0.878 units on a scale | Standard Error 0.097 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Week 5 | -0.840 units on a scale | Standard Error 0.104 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Week 8 | -1.158 units on a scale | Standard Error 0.107 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Week 1 | -0.389 units on a scale | Standard Error 0.078 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Week 2 | -0.589 units on a scale | Standard Error 0.095 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Week 3 | -0.890 units on a scale | Standard Error 0.092 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Week 4 | -0.914 units on a scale | Standard Error 0.099 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Week 5 | -0.972 units on a scale | Standard Error 0.107 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Week 6 | -1.026 units on a scale | Standard Error 0.107 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity' | Week 7 | -1.063 units on a scale | Standard Error 0.112 |
Comparison: Week 1p-value: 0.192295% CI: [-0.072, 0.357]ANCOVA
Comparison: Week 1p-value: 0.509195% CI: [-0.143, 0.288]ANCOVA
Comparison: Week 1p-value: 0.739495% CI: [-0.181, 0.254]ANCOVA
Comparison: Week 2p-value: 0.584595% CI: [-0.189, 0.334]ANCOVA
Comparison: Week 2p-value: 0.795995% CI: [-0.296, 0.228]ANCOVA
Comparison: Week 2p-value: 0.908695% CI: [-0.28, 0.249]ANCOVA
Comparison: Week 3p-value: 0.533495% CI: [-0.333, 0.173]ANCOVA
Comparison: Week 3p-value: 0.10295% CI: [-0.466, 0.042]ANCOVA
Comparison: Week 3p-value: 0.006695% CI: [-0.613, -0.1]ANCOVA
Comparison: Week 4p-value: 0.358695% CI: [-0.399, 0.145]ANCOVA
Comparison: Week 4p-value: 0.012895% CI: [-0.621, -0.075]ANCOVA
Comparison: Week 4p-value: 0.006495% CI: [-0.66, -0.109]ANCOVA
Comparison: Week 5p-value: 0.612495% CI: [-0.369, 0.218]ANCOVA
Comparison: Week 5p-value: 0.136595% CI: [-0.518, 0.071]ANCOVA
Comparison: Week 5p-value: 0.019395% CI: [-0.652, -0.058]ANCOVA
Comparison: Week 6p-value: 0.804695% CI: [-0.333, 0.258]ANCOVA
Comparison: Week 6p-value: 0.03595% CI: [-0.616, -0.023]ANCOVA
Comparison: Week 6p-value: 0.010595% CI: [-0.691, -0.093]ANCOVA
Comparison: Week 7p-value: 0.548295% CI: [-0.403, 0.214]ANCOVA
Comparison: Week 7p-value: 0.01795% CI: [-0.687, -0.068]ANCOVA
Comparison: Week 7p-value: 0.003495% CI: [-0.781, -0.157]ANCOVA
Comparison: Week 8p-value: 0.534695% CI: [-0.388, 0.202]ANCOVA
Comparison: Week 8p-value: 0.026295% CI: [-0.632, -0.04]ANCOVA
Comparison: Week 8p-value: 0.000495% CI: [-0.843, -0.246]ANCOVA
Secondary
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
Population: modified Intent-to-Treat Population: all randomized participants who received at least one dose of study treatment with values at both baseline and treatment week.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Week 1 | -0.498 units on a scale | Standard Error 0.075 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Week 2 | -0.618 units on a scale | Standard Error 0.088 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Week 3 | -0.671 units on a scale | Standard Error 0.094 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Week 4 | -0.737 units on a scale | Standard Error 0.098 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Week 5 | -0.824 units on a scale | Standard Error 0.098 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Week 6 | -0.883 units on a scale | Standard Error 0.102 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Week 7 | -0.849 units on a scale | Standard Error 0.107 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Week 8 | -0.864 units on a scale | Standard Error 0.107 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Week 6 | -0.805 units on a scale | Standard Error 0.1 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Week 5 | -0.850 units on a scale | Standard Error 0.096 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Week 2 | -0.566 units on a scale | Standard Error 0.086 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Week 8 | -0.822 units on a scale | Standard Error 0.105 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Week 7 | -0.756 units on a scale | Standard Error 0.105 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Week 4 | -0.763 units on a scale | Standard Error 0.096 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Week 3 | -0.675 units on a scale | Standard Error 0.092 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Week 1 | -0.405 units on a scale | Standard Error 0.074 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Week 7 | -0.906 units on a scale | Standard Error 0.106 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Week 3 | -0.817 units on a scale | Standard Error 0.092 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Week 4 | -0.810 units on a scale | Standard Error 0.096 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Week 5 | -0.846 units on a scale | Standard Error 0.096 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Week 6 | -0.961 units on a scale | Standard Error 0.1 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Week 8 | -0.989 units on a scale | Standard Error 0.105 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Week 1 | -0.309 units on a scale | Standard Error 0.074 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Week 2 | -0.611 units on a scale | Standard Error 0.087 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Week 3 | -1.022 units on a scale | Standard Error 0.094 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Week 4 | -1.061 units on a scale | Standard Error 0.098 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Week 2 | -0.714 units on a scale | Standard Error 0.088 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Week 1 | -0.519 units on a scale | Standard Error 0.076 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Week 5 | -1.156 units on a scale | Standard Error 0.098 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Week 8 | -1.197 units on a scale | Standard Error 0.107 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Week 7 | -1.166 units on a scale | Standard Error 0.108 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity' | Week 6 | -1.174 units on a scale | Standard Error 0.102 |
Comparison: Week 1p-value: 0.378895% CI: [-0.114, 0.3]ANCOVA
Comparison: Week 1p-value: 0.076195% CI: [-0.02, 0.397]ANCOVA
Comparison: Week 1p-value: 0.841595% CI: [-0.232, 0.189]ANCOVA
Comparison: Week 2p-value: 0.671995% CI: [-0.19, 0.294]ANCOVA
Comparison: Week 2p-value: 0.954995% CI: [-0.237, 0.251]ANCOVA
Comparison: Week 2p-value: 0.440895% CI: [-0.342, 0.149]ANCOVA
Comparison: Week 3p-value: 0.973695% CI: [-0.262, 0.253]ANCOVA
Comparison: Week 3p-value: 0.270395% CI: [-0.405, 0.114]ANCOVA
Comparison: Week 3p-value: 0.008795% CI: [-0.612, -0.089]ANCOVA
Comparison: Week 4p-value: 0.84895% CI: [-0.295, 0.243]ANCOVA
Comparison: Week 4p-value: 0.596695% CI: [-0.344, 0.198]ANCOVA
Comparison: Week 4p-value: 0.020395% CI: [-0.596, -0.051]ANCOVA
Comparison: Week 5p-value: 0.85495% CI: [-0.294, 0.244]ANCOVA
Comparison: Week 5p-value: 0.875795% CI: [-0.293, 0.25]ANCOVA
Comparison: Week 5p-value: 0.017495% CI: [-0.605, -0.059]ANCOVA
Comparison: Week 6p-value: 0.583195% CI: [-0.202, 0.358]ANCOVA
Comparison: Week 6p-value: 0.585995% CI: [-0.36, 0.204]ANCOVA
Comparison: Week 6p-value: 0.044795% CI: [-0.575, -0.007]ANCOVA
Comparison: Week 7p-value: 0.536595% CI: [-0.203, 0.388]ANCOVA
Comparison: Week 7p-value: 0.706795% CI: [-0.355, 0.241]ANCOVA
Comparison: Week 7p-value: 0.038695% CI: [-0.616, -0.017]ANCOVA
Comparison: Week 8p-value: 0.780495% CI: [-0.253, 0.336]ANCOVA
Comparison: Week 8p-value: 0.406495% CI: [-0.422, 0.171]ANCOVA
Comparison: Week 8p-value: 0.028995% CI: [-0.632, -0.035]ANCOVA
Secondary
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
Population: modified Intent-to-Treat Population: all randomized participants who received at least one dose of study treatment with values at both baseline and treatment week.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Week 1 | -0.329 units on a scale | Standard Error 0.074 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Week 2 | -0.483 units on a scale | Standard Error 0.09 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Week 3 | -0.526 units on a scale | Standard Error 0.095 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Week 4 | -0.505 units on a scale | Standard Error 0.102 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Week 5 | -0.588 units on a scale | Standard Error 0.107 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Week 6 | -0.617 units on a scale | Standard Error 0.11 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Week 7 | -0.570 units on a scale | Standard Error 0.111 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Week 8 | -0.604 units on a scale | Standard Error 0.108 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Week 6 | -0.677 units on a scale | Standard Error 0.108 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Week 5 | -0.684 units on a scale | Standard Error 0.106 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Week 2 | -0.416 units on a scale | Standard Error 0.089 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Week 8 | -0.683 units on a scale | Standard Error 0.107 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Week 7 | -0.626 units on a scale | Standard Error 0.109 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Week 4 | -0.631 units on a scale | Standard Error 0.101 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Week 3 | -0.574 units on a scale | Standard Error 0.094 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Week 1 | -0.292 units on a scale | Standard Error 0.073 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Week 7 | -0.860 units on a scale | Standard Error 0.109 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Week 3 | -0.796 units on a scale | Standard Error 0.094 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Week 4 | -0.842 units on a scale | Standard Error 0.101 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Week 5 | -0.870 units on a scale | Standard Error 0.106 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Week 6 | -0.990 units on a scale | Standard Error 0.108 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Week 8 | -0.954 units on a scale | Standard Error 0.107 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Week 1 | -0.400 units on a scale | Standard Error 0.073 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Week 2 | -0.605 units on a scale | Standard Error 0.089 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Week 3 | -0.778 units on a scale | Standard Error 0.096 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Week 4 | -0.833 units on a scale | Standard Error 0.103 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Week 2 | -0.544 units on a scale | Standard Error 0.091 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Week 1 | -0.406 units on a scale | Standard Error 0.074 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Week 5 | -0.842 units on a scale | Standard Error 0.108 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Week 8 | -1.086 units on a scale | Standard Error 0.109 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Week 7 | -1.054 units on a scale | Standard Error 0.111 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity' | Week 6 | -0.962 units on a scale | Standard Error 0.11 |
Comparison: Week 1p-value: 0.720795% CI: [-0.167, 0.241]ANCOVA
Comparison: Week 1p-value: 0.494695% CI: [-0.275, 0.133]ANCOVA
Comparison: Week 1p-value: 0.459695% CI: [-0.283, 0.129]ANCOVA
Comparison: Week 2p-value: 0.598795% CI: [-0.182, 0.315]ANCOVA
Comparison: Week 2p-value: 0.334895% CI: [-0.372, 0.127]ANCOVA
Comparison: Week 2p-value: 0.628895% CI: [-0.313, 0.19]ANCOVA
Comparison: Week 3p-value: 0.719395% CI: [-0.312, 0.216]ANCOVA
Comparison: Week 3p-value: 0.045295% CI: [-0.534, -0.006]ANCOVA
Comparison: Week 3p-value: 0.063595% CI: [-0.519, 0.014]ANCOVA
Comparison: Week 4p-value: 0.3895% CI: [-0.409, 0.156]ANCOVA
Comparison: Week 4p-value: 0.0295% CI: [-0.62, -0.053]ANCOVA
Comparison: Week 4p-value: 0.024495% CI: [-0.614, -0.043]ANCOVA
Comparison: Week 5p-value: 0.523295% CI: [-0.392, 0.2]ANCOVA
Comparison: Week 5p-value: 0.062395% CI: [-0.579, 0.015]ANCOVA
Comparison: Week 5p-value: 0.095195% CI: [-0.554, 0.045]ANCOVA
Comparison: Week 8p-value: 0.001995% CI: [-0.785, -0.18]ANCOVA
Comparison: Week 6p-value: 0.698595% CI: [-0.363, 0.243]ANCOVA
Comparison: Week 6p-value: 0.016395% CI: [-0.677, -0.069]ANCOVA
Comparison: Week 6p-value: 0.027395% CI: [-0.652, -0.039]ANCOVA
Comparison: Week 7p-value: 0.718795% CI: [-0.362, 0.25]ANCOVA
Comparison: Week 7p-value: 0.06495% CI: [-0.596, 0.017]ANCOVA
Comparison: Week 7p-value: 0.002395% CI: [-0.793, -0.175]ANCOVA
Comparison: Week 8p-value: 0.603395% CI: [-0.378, 0.22]ANCOVA
Comparison: Week 8p-value: 0.022295% CI: [-0.65, -0.05]ANCOVA
Secondary
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
Population: modified Intent-to-Treat Population: all randomized participants who received at least one dose of study treatment with values at both baseline and treatment week.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Week 1 | -0.602 units on a scale | Standard Error 0.089 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Week 5 | -1.279 units on a scale | Standard Error 0.119 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Week 8 | -1.289 units on a scale | Standard Error 0.121 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Week 2 | -0.921 units on a scale | Standard Error 0.103 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Week 6 | -1.343 units on a scale | Standard Error 0.118 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Week 3 | -1.002 units on a scale | Standard Error 0.11 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Week 4 | -1.185 units on a scale | Standard Error 0.113 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Week 7 | -1.252 units on a scale | Standard Error 0.122 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Week 1 | -0.548 units on a scale | Standard Error 0.088 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Week 4 | -1.210 units on a scale | Standard Error 0.111 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Week 5 | -1.230 units on a scale | Standard Error 0.117 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Week 3 | -1.008 units on a scale | Standard Error 0.108 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Week 7 | -1.303 units on a scale | Standard Error 0.121 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Week 8 | -1.333 units on a scale | Standard Error 0.119 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Week 6 | -1.257 units on a scale | Standard Error 0.117 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Week 2 | -0.869 units on a scale | Standard Error 0.101 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Week 6 | -1.367 units on a scale | Standard Error 0.117 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Week 7 | -1.302 units on a scale | Standard Error 0.121 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Week 2 | -0.934 units on a scale | Standard Error 0.102 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Week 8 | -1.525 units on a scale | Standard Error 0.119 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Week 3 | -1.126 units on a scale | Standard Error 0.109 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Week 1 | -0.454 units on a scale | Standard Error 0.089 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Week 4 | -1.244 units on a scale | Standard Error 0.112 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Week 5 | -1.299 units on a scale | Standard Error 0.118 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Week 8 | -1.674 units on a scale | Standard Error 0.122 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Week 1 | -0.626 units on a scale | Standard Error 0.09 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Week 2 | -1.083 units on a scale | Standard Error 0.103 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Week 3 | -1.313 units on a scale | Standard Error 0.111 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Week 4 | -1.439 units on a scale | Standard Error 0.114 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Week 5 | -1.578 units on a scale | Standard Error 0.12 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Week 6 | -1.665 units on a scale | Standard Error 0.119 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity' | Week 7 | -1.638 units on a scale | Standard Error 0.124 |
Comparison: Week 1p-value: 0.666395% CI: [-0.193, 0.301]ANCOVA
Comparison: Week 1p-value: 0.2495% CI: [-0.1, 0.396]ANCOVA
Comparison: Week 1p-value: 0.85695% CI: [-0.273, 0.227]ANCOVA
Comparison: Week 2p-value: 0.720995% CI: [-0.232, 0.335]ANCOVA
Comparison: Week 2p-value: 0.928395% CI: [-0.297, 0.271]ANCOVA
Comparison: Week 2p-value: 0.265995% CI: [-0.449, 0.124]ANCOVA
Comparison: Week 3p-value: 0.96895% CI: [-0.31, 0.298]ANCOVA
Comparison: Week 3p-value: 0.421395% CI: [-0.429, 0.18]ANCOVA
Comparison: Week 3p-value: 0.047195% CI: [-0.618, -0.004]ANCOVA
Comparison: Week 4p-value: 0.876995% CI: [-0.337, 0.288]ANCOVA
Comparison: Week 4p-value: 0.710995% CI: [-0.372, 0.254]ANCOVA
Comparison: Week 4p-value: 0.114695% CI: [-0.57, 0.062]ANCOVA
Comparison: Week 5p-value: 0.773695% CI: [-0.281, 0.378]ANCOVA
Comparison: Week 5p-value: 0.905995% CI: [-0.35, 0.31]ANCOVA
Comparison: Week 5p-value: 0.077995% CI: [-0.633, 0.034]ANCOVA
Comparison: Week 6p-value: 0.606895% CI: [-0.241, 0.412]ANCOVA
Comparison: Week 5p-value: 0.883895% CI: [-0.352, 0.303]ANCOVA
Comparison: Week 6p-value: 0.055695% CI: [-0.653, 0.008]ANCOVA
Comparison: Week 7p-value: 0.767395% CI: [-0.389, 0.287]ANCOVA
Comparison: Week 7p-value: 0.770995% CI: [-0.389, 0.289]ANCOVA
Comparison: Week 7p-value: 0.027395% CI: [-0.728, -0.043]ANCOVA
Comparison: Week 8p-value: 0.79595% CI: [-0.378, 0.289]ANCOVA
Comparison: Week 8p-value: 0.165695% CI: [-0.57, 0.098]ANCOVA
Comparison: Week 8p-value: 0.025495% CI: [-0.722, -0.048]ANCOVA
Secondary
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
Population: modified Intent-to-Treat Population: all randomized participants who received at least one dose of study treatment with values at both baseline and treatment week.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Week 3 | -0.581 units on a scale | Standard Error 0.084 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Week 1 | -0.483 units on a scale | Standard Error 0.067 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Week 2 | -0.647 units on a scale | Standard Error 0.082 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Week 4 | -0.769 units on a scale | Standard Error 0.089 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Week 5 | -0.758 units on a scale | Standard Error 0.087 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Week 6 | -0.834 units on a scale | Standard Error 0.09 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Week 7 | -0.796 units on a scale | Standard Error 0.09 |
| Placebo BID | Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Week 8 | -0.811 units on a scale | Standard Error 0.092 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Week 6 | -0.936 units on a scale | Standard Error 0.089 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Week 5 | -0.869 units on a scale | Standard Error 0.086 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Week 2 | -0.637 units on a scale | Standard Error 0.081 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Week 8 | -0.951 units on a scale | Standard Error 0.091 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Week 1 | -0.385 units on a scale | Standard Error 0.066 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Week 4 | -0.855 units on a scale | Standard Error 0.088 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Week 3 | -0.784 units on a scale | Standard Error 0.083 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Week 7 | -0.899 units on a scale | Standard Error 0.089 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Week 2 | -0.597 units on a scale | Standard Error 0.081 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Week 3 | -0.791 units on a scale | Standard Error 0.083 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Week 4 | -0.838 units on a scale | Standard Error 0.087 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Week 5 | -0.866 units on a scale | Standard Error 0.085 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Week 6 | -0.939 units on a scale | Standard Error 0.089 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Week 8 | -1.029 units on a scale | Standard Error 0.091 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Week 1 | -0.340 units on a scale | Standard Error 0.066 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Week 7 | -0.867 units on a scale | Standard Error 0.089 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Week 2 | -0.774 units on a scale | Standard Error 0.083 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Week 4 | -0.984 units on a scale | Standard Error 0.089 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Week 7 | -1.081 units on a scale | Standard Error 0.091 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Week 3 | -0.879 units on a scale | Standard Error 0.085 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Week 5 | -1.028 units on a scale | Standard Error 0.087 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Week 8 | -1.191 units on a scale | Standard Error 0.093 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Week 1 | -0.511 units on a scale | Standard Error 0.068 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency' | Week 6 | -1.093 units on a scale | Standard Error 0.09 |
Comparison: Week 1p-value: 0.300795% CI: [-0.088, 0.284]ANCOVA
Comparison: Week 1p-value: 0.129595% CI: [-0.042, 0.328]ANCOVA
Comparison: Week 1p-value: 0.767195% CI: [-0.216, 0.159]ANCOVA
Comparison: Week 2p-value: 0.930895% CI: [-0.217, 0.238]ANCOVA
Comparison: Week 2p-value: 0.659595% CI: [-0.176, 0.277]ANCOVA
Comparison: Week 2p-value: 0.277195% CI: [-0.356, 0.102]ANCOVA
Comparison: Week 3p-value: 0.088795% CI: [-0.436, 0.031]ANCOVA
Comparison: Week 3p-value: 0.075895% CI: [-0.443, 0.022]ANCOVA
Comparison: Week 3p-value: 0.013295% CI: [-0.534, -0.063]ANCOVA
Comparison: Week 4p-value: 0.490395% CI: [-0.332, 0.16]ANCOVA
Comparison: Week 4p-value: 0.582495% CI: [-0.313, 0.176]ANCOVA
Comparison: Week 4p-value: 0.088595% CI: [-0.463, 0.033]ANCOVA
Comparison: Week 5p-value: 0.365295% CI: [-0.352, 0.13]ANCOVA
Comparison: Week 5p-value: 0.373995% CI: [-0.348, 0.131]ANCOVA
Comparison: Week 5p-value: 0.029495% CI: [-0.512, -0.027]ANCOVA
Comparison: Week 6p-value: 0.423695% CI: [-0.351, 0.148]ANCOVA
Comparison: Week 6p-value: 0.407195% CI: [-0.353, 0.144]ANCOVA
Comparison: Week 6p-value: 0.043495% CI: [-0.51, -0.008]ANCOVA
Comparison: Week 7p-value: 0.417295% CI: [-0.354, 0.147]ANCOVA
Comparison: Week 7p-value: 0.575995% CI: [-0.321, 0.179]ANCOVA
Comparison: Week 7p-value: 0.027195% CI: [-0.538, -0.033]ANCOVA
Comparison: Week 8p-value: 0.280495% CI: [-0.395, 0.115]ANCOVA
Comparison: Week 8p-value: 0.091395% CI: [-0.472, 0.035]ANCOVA
Comparison: Week 8p-value: 0.003995% CI: [-0.637, -0.123]ANCOVA
Secondary
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
Population: modified Intent-to-Treat Population: all randomized participants who received at least one dose of study treatment with values at both baseline and treatment week.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Week 3 | -1.092 units on a scale | Standard Error 0.109 |
| Placebo BID | Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Week 6 | -1.396 units on a scale | Standard Error 0.121 |
| Placebo BID | Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Week 1 | -0.655 units on a scale | Standard Error 0.09 |
| Placebo BID | Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Week 2 | -0.994 units on a scale | Standard Error 0.102 |
| Placebo BID | Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Week 4 | -1.263 units on a scale | Standard Error 0.112 |
| Placebo BID | Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Week 5 | -1.284 units on a scale | Standard Error 0.12 |
| Placebo BID | Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Week 7 | -1.392 units on a scale | Standard Error 0.127 |
| Placebo BID | Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Week 8 | -1.404 units on a scale | Standard Error 0.127 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Week 5 | -1.301 units on a scale | Standard Error 0.119 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Week 3 | -1.141 units on a scale | Standard Error 0.107 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Week 4 | -1.281 units on a scale | Standard Error 0.11 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Week 6 | -1.343 units on a scale | Standard Error 0.119 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Week 8 | -1.482 units on a scale | Standard Error 0.126 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Week 2 | -0.974 units on a scale | Standard Error 0.101 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Week 7 | -1.350 units on a scale | Standard Error 0.125 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Week 1 | -0.632 units on a scale | Standard Error 0.089 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Week 7 | -1.436 units on a scale | Standard Error 0.125 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Week 2 | -0.977 units on a scale | Standard Error 0.101 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Week 1 | -0.531 units on a scale | Standard Error 0.089 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Week 4 | -1.259 units on a scale | Standard Error 0.11 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Week 5 | -1.339 units on a scale | Standard Error 0.119 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Week 3 | -1.153 units on a scale | Standard Error 0.107 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Week 6 | -1.467 units on a scale | Standard Error 0.119 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Week 8 | -1.666 units on a scale | Standard Error 0.126 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Week 6 | -1.744 units on a scale | Standard Error 0.122 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Week 8 | -1.807 units on a scale | Standard Error 0.128 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Week 5 | -1.677 units on a scale | Standard Error 0.121 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Week 1 | -0.673 units on a scale | Standard Error 0.091 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Week 7 | -1.693 units on a scale | Standard Error 0.128 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Week 2 | -1.102 units on a scale | Standard Error 0.103 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Week 3 | -1.350 units on a scale | Standard Error 0.109 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity' | Week 4 | -1.498 units on a scale | Standard Error 0.112 |
Comparison: Week 1p-value: 0.85695% CI: [-0.226, 0.272]ANCOVA
Comparison: Week 1p-value: 0.330195% CI: [-0.126, 0.373]ANCOVA
Comparison: Week 1p-value: 0.884595% CI: [-0.27, 0.233]ANCOVA
Comparison: Week 2p-value: 0.887995% CI: [-0.262, 0.303]ANCOVA
Comparison: Week 2p-value: 0.907295% CI: [-0.266, 0.299]ANCOVA
Comparison: Week 2p-value: 0.457395% CI: [-0.393, 0.177]ANCOVA
Comparison: Week 3p-value: 0.747695% CI: [-0.35, 0.251]ANCOVA
Comparison: Week 3p-value: 0.687395% CI: [-0.362, 0.239]ANCOVA
Comparison: Week 3p-value: 0.095295% CI: [-0.562, 0.045]ANCOVA
Comparison: Week 4p-value: 0.911195% CI: [-0.326, 0.291]ANCOVA
Comparison: Week 4p-value: 0.977295% CI: [-0.304, 0.313]ANCOVA
Comparison: Week 4p-value: 0.13995% CI: [-0.546, 0.077]ANCOVA
Comparison: Week 5p-value: 0.921595% CI: [-0.349, 0.316]ANCOVA
Comparison: Week 5p-value: 0.745395% CI: [-0.388, 0.278]ANCOVA
Comparison: Week 5p-value: 0.02295% CI: [-0.729, -0.057]ANCOVA
Comparison: Week 6p-value: 0.756195% CI: [-0.282, 0.387]ANCOVA
Comparison: Week 6p-value: 0.675895% CI: [-0.406, 0.263]ANCOVA
Comparison: Week 6p-value: 0.043495% CI: [-0.686, -0.01]ANCOVA
Comparison: Week 7p-value: 0.812395% CI: [-0.308, 0.392]ANCOVA
Comparison: Week 7p-value: 0.803895% CI: [-0.394, 0.306]ANCOVA
Comparison: Week 7p-value: 0.095495% CI: [-0.654, 0.053]ANCOVA
Comparison: Week 8p-value: 0.664995% CI: [-0.43, 0.275]ANCOVA
Comparison: Week 8p-value: 0.144895% CI: [-0.614, 0.091]ANCOVA
Comparison: Week 8p-value: 0.026495% CI: [-0.759, -0.048]ANCOVA
Secondary
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
Population: modified Intent-to-Treat Population: all randomized participants who received at least one dose of study treatment with values at both baseline and treatment week.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Week 2 | -0.998 units on a scale | Standard Error 0.103 |
| Placebo BID | Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Week 1 | -0.638 units on a scale | Standard Error 0.089 |
| Placebo BID | Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Week 4 | -1.199 units on a scale | Standard Error 0.113 |
| Placebo BID | Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Week 3 | -1.040 units on a scale | Standard Error 0.108 |
| Placebo BID | Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Week 7 | -1.310 units on a scale | Standard Error 0.124 |
| Placebo BID | Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Week 8 | -1.329 units on a scale | Standard Error 0.122 |
| Placebo BID | Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Week 6 | -1.357 units on a scale | Standard Error 0.119 |
| Placebo BID | Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Week 5 | -1.226 units on a scale | Standard Error 0.12 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Week 4 | -1.246 units on a scale | Standard Error 0.112 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Week 2 | -0.918 units on a scale | Standard Error 0.101 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Week 5 | -1.287 units on a scale | Standard Error 0.118 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Week 1 | -0.536 units on a scale | Standard Error 0.087 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Week 3 | -1.074 units on a scale | Standard Error 0.106 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Week 6 | -1.297 units on a scale | Standard Error 0.117 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Week 7 | -1.359 units on a scale | Standard Error 0.122 |
| 500 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Week 8 | -1.422 units on a scale | Standard Error 0.12 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Week 4 | -1.316 units on a scale | Standard Error 0.112 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Week 1 | -0.492 units on a scale | Standard Error 0.088 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Week 8 | -1.627 units on a scale | Standard Error 0.121 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Week 7 | -1.424 units on a scale | Standard Error 0.122 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Week 6 | -1.450 units on a scale | Standard Error 0.117 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Week 3 | -1.112 units on a scale | Standard Error 0.107 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Week 5 | -1.323 units on a scale | Standard Error 0.118 |
| 1000 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Week 2 | -0.970 units on a scale | Standard Error 0.102 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Week 2 | -1.116 units on a scale | Standard Error 0.104 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Week 4 | -1.497 units on a scale | Standard Error 0.114 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Week 1 | -0.675 units on a scale | Standard Error 0.089 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Week 5 | -1.648 units on a scale | Standard Error 0.121 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Week 8 | -1.781 units on a scale | Standard Error 0.123 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Week 6 | -1.733 units on a scale | Standard Error 0.12 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Week 7 | -1.676 units on a scale | Standard Error 0.125 |
| 1500 mg IW-3718 BID | Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity' | Week 3 | -1.385 units on a scale | Standard Error 0.109 |
Comparison: Week 1p-value: 0.413795% CI: [-0.143, 0.347]ANCOVA
Comparison: Week 1p-value: 0.239595% CI: [-0.098, 0.392]ANCOVA
Comparison: Week 1p-value: 0.772995% CI: [-0.284, 0.212]ANCOVA
Comparison: Week 2p-value: 0.582495% CI: [-0.205, 0.363]ANCOVA
Comparison: Week 2p-value: 0.846695% CI: [-0.256, 0.312]ANCOVA
Comparison: Week 2p-value: 0.419295% CI: [-0.405, 0.169]ANCOVA
Comparison: Week 3p-value: 0.819295% CI: [-0.333, 0.264]ANCOVA
Comparison: Week 3p-value: 0.63295% CI: [-0.372, 0.226]ANCOVA
Comparison: Week 3p-value: 0.025495% CI: [-0.647, -0.043]ANCOVA
Comparison: Week 4p-value: 0.768995% CI: [-0.36, 0.266]ANCOVA
Comparison: Week 4p-value: 0.463195% CI: [-0.43, 0.196]ANCOVA
Comparison: Week 4p-value: 0.065195% CI: [-0.615, 0.019]ANCOVA
Comparison: Week 5p-value: 0.719795% CI: [-0.392, 0.271]ANCOVA
Comparison: Week 5p-value: 0.564995% CI: [-0.428, 0.234]ANCOVA
Comparison: Week 5p-value: 0.013895% CI: [-0.757, -0.087]ANCOVA
Comparison: Week 6p-value: 0.720295% CI: [-0.269, 0.388]ANCOVA
Comparison: Week 6p-value: 0.578495% CI: [-0.421, 0.236]ANCOVA
Comparison: Week 6p-value: 0.026695% CI: [-0.708, -0.044]ANCOVA
Comparison: Week 7p-value: 0.77795% CI: [-0.391, 0.293]ANCOVA
Comparison: Week 7p-value: 0.512195% CI: [-0.456, 0.228]ANCOVA
Comparison: Week 7p-value: 0.038495% CI: [-0.711, -0.02]ANCOVA
Comparison: Week 8p-value: 0.587695% CI: [-0.431, 0.245]ANCOVA
Comparison: Week 8p-value: 0.084295% CI: [-0.636, 0.04]ANCOVA
Comparison: Week 8p-value: 0.009895% CI: [-0.793, -0.11]ANCOVA
Secondary
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
Population: modified Intent-to-Treat Population: all randomized participants who received at least one dose of study treatment with values both at baseline and during the Treatment Period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo BID | Change From Baseline to Week 4 in WHSS | -1.261 score on a scale | Standard Error 0.115 |
| 500 mg IW-3718 BID | Change From Baseline to Week 4 in WHSS | -1.313 score on a scale | Standard Error 0.113 |
| 1000 mg IW-3718 BID | Change From Baseline to Week 4 in WHSS | -1.308 score on a scale | Standard Error 0.113 |
| 1500 mg IW-3718 BID | Change From Baseline to Week 4 in WHSS | -1.517 score on a scale | Standard Error 0.115 |
p-value: 0.74795% CI: [-0.369, 0.265]ANCOVA
p-value: 0.769995% CI: [-0.364, 0.27]ANCOVA
p-value: 0.115795% CI: [-0.577, 0.064]ANCOVA
p-value: 0.1374trend test
Secondary
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
Population: modified Intent-to-Treat Population: all randomized participants who received at least one dose of study treatment with values both at baseline and during the Treatment Period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo BID | Change From Baseline to Week 8 in WHSS | -1.459 score on a scale | Standard Error 0.129 |
| 500 mg IW-3718 BID | Change From Baseline to Week 8 in WHSS | -1.517 score on a scale | Standard Error 0.127 |
| 1000 mg IW-3718 BID | Change From Baseline to Week 8 in WHSS | -1.713 score on a scale | Standard Error 0.127 |
| 1500 mg IW-3718 BID | Change From Baseline to Week 8 in WHSS | -1.876 score on a scale | Standard Error 0.13 |
p-value: 0.748895% CI: [-0.415, 0.299]ANCOVA
p-value: 0.162795% CI: [-0.611, 0.103]ANCOVA
p-value: 0.023795% CI: [-0.777, -0.056]ANCOVA
p-value: 0.013trend test
Secondary
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
Population: modified Intent-to-Treat Population: all randomized participants who received at least one dose of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo BID | Percentage of Participants Who Are Overall Heartburn Responders | 54.3 percentage of participants |
| 500 mg IW-3718 BID | Percentage of Participants Who Are Overall Heartburn Responders | 52.1 percentage of participants |
| 1000 mg IW-3718 BID | Percentage of Participants Who Are Overall Heartburn Responders | 62.0 percentage of participants |
| 1500 mg IW-3718 BID | Percentage of Participants Who Are Overall Heartburn Responders | 66.2 percentage of participants |
p-value: 0.790395% CI: [0.47, 1.77]Cochran-Mantel-Haenszel
p-value: 0.351895% CI: [0.7, 2.71]Cochran-Mantel-Haenszel
p-value: 0.154495% CI: [0.83, 3.26]Cochran-Mantel-Haenszel
Secondary
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
Population: modified Intent-to-Treat Population: all randomized participants who received at least one dose of study treatment with values at both baseline and given treatment week.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo BID | Percentage of Participants With a DHSS of No More Than Very Mild (≤ 1) on Any Day During Week 4 | 12.9 percentage of participants |
| 500 mg IW-3718 BID | Percentage of Participants With a DHSS of No More Than Very Mild (≤ 1) on Any Day During Week 4 | 15.5 percentage of participants |
| 1000 mg IW-3718 BID | Percentage of Participants With a DHSS of No More Than Very Mild (≤ 1) on Any Day During Week 4 | 22.5 percentage of participants |
| 1500 mg IW-3718 BID | Percentage of Participants With a DHSS of No More Than Very Mild (≤ 1) on Any Day During Week 4 | 22.1 percentage of participants |
p-value: 0.656695% CI: [0.48, 3.18]Cochran-Mantel-Haenszel
p-value: 0.12895% CI: [0.81, 4.98]Cochran-Mantel-Haenszel
p-value: 0.146395% CI: [0.79, 4.91]Cochran-Mantel-Haenszel
Secondary
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
Population: modified Intent-to-Treat Population: all randomized participants who received at least one dose of study treatment with values both at baseline and given treatment week.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo BID | Percentage of Participants With a DHSS of No More Than Very Mild (≤ 1) on Any Day During Week 8 | 28.6 percentage of participants |
| 500 mg IW-3718 BID | Percentage of Participants With a DHSS of No More Than Very Mild (≤ 1) on Any Day During Week 8 | 18.3 percentage of participants |
| 1000 mg IW-3718 BID | Percentage of Participants With a DHSS of No More Than Very Mild (≤ 1) on Any Day During Week 8 | 29.6 percentage of participants |
| 1500 mg IW-3718 BID | Percentage of Participants With a DHSS of No More Than Very Mild (≤ 1) on Any Day During Week 8 | 38.2 percentage of participants |
p-value: 0.148995% CI: [0.25, 1.23]Cochran-Mantel-Haenszel
p-value: 0.889195% CI: [0.51, 2.19]Cochran-Mantel-Haenszel
p-value: 0.223795% CI: [0.76, 3.2]Cochran-Mantel-Haenszel
Secondary
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
Population: modified Intent-to-Treat Population: all randomized participants who received at least one dose of study treatment with values both at baseline and during the Treatment Period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo BID | Percent Change From Baseline to Week 4 in WHSS | -38.883 percentage change in score | Standard Error 3.733 |
| 500 mg IW-3718 BID | Percent Change From Baseline to Week 4 in WHSS | -42.594 percentage change in score | Standard Error 3.679 |
| 1000 mg IW-3718 BID | Percent Change From Baseline to Week 4 in WHSS | -41.622 percentage change in score | Standard Error 3.683 |
| 1500 mg IW-3718 BID | Percent Change From Baseline to Week 4 in WHSS | -47.486 percentage change in score | Standard Error 3.761 |
p-value: 0.479595% CI: [-14.028, 6.606]ANCOVA
p-value: 0.60295% CI: [-13.066, 7.588]ANCOVA
p-value: 0.105595% CI: [-19.03, 1.826]ANCOVA
p-value: 0.1387trend test