Non-erosive Gastroesophageal Reflux Disease
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study was to evaluate the efficacy and safety of oral TAK-438 10 mg once-daily in the treatment of non-erosive gastroesophageal reflux disease (NERD).
Detailed description
A phase 3, randomized, double-blind, placebo-controlled, parallel-group, multi-center study will be conducted to verify the superiority of TAK-438 (TAK-438 10 mg, once daily, 4 weeks) to placebo (placebo, once daily, 4 weeks) in participants with non-erosive gastroesophageal reflux disease (NERD). The study consists of a 1-week, single-blind run-in period and a 4-week, double-blind treatment period. The participants will receive the study drug (TAK-438 placebo tablet) for the 1-week single-blind run-in period. After the run-in period, eligible participants will be randomized into TAK-438 10 mg or placebo treatment groups in a 1:1 ratio. The randomized participants will receive the assigned study drug (TAK-438 10 mg tablet or placebo tablet) for the 4-week double-blind treatment period.
Interventions
DRUGPlacebo
TAK-438 placebo-matching tablets
DRUGTAK-438 10 mg
TAK-438 tablets
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements. 2. The participant signs and dates a written informed consent form prior to the initiation of any study procedures. 3. The participant with NERD. 4. The participant is endoscopically confirmed to have the modified Los Angeles (LA) Classification Grade N or M at the start of the run-in period (Visit 1). To allow efficacy evaluation in the participants with Grade N as well as in those with Grade M, the target number of participants in each grade is at least 30% of the total number of participants. Enrollment of patients with either Grade N or M will end when the number of enrolled participants with each grade exceeds 332, or 70% of the total planned number of participants. 5. The participant experiences recurrent heartburn, on at least 2 days a week over the last 3 weeks prior to the start of the run-in period (Visit 1). 6. The participant is either a male or female outpatient with a minimum age of 20 years at the time of informed consent signing. However, participants who are hospitalized only for examination purposes are also allowed to participate. 7. A female participant of childbearing potential agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study, and for 4 weeks after the last dose of study drug. 8. The participant's compliance to the study drug has been good (75% or better) in the run-in period. 9. The participant has experienced heartburn on at least 2 days in the last 1 week prior to randomization. 10. The participant has appropriately provided in the patient's diary all the required information during the run-in period.
Exclusion criteria
1. The participant has received any investigational compound within 84 days prior to the first dose of study drug. 2. The participant has received TAK-438 in a previous clinical study or as a therapeutic agent, except one with experience of receiving TAK-438 as an adjunct therapy for H. pylori eradication, who can be enrolled in this study. 3. The participant is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress. 4. The participant has donated at least 400 mL of blood within the 90 days prior to the start of the run-in period (Visit 1). 5. Endoscopic examination for entering this study fails to diagnose NERD within 84 days before the start of the run-in period (Visit 1). 6. The participant has any complications affecting the esophagus, including Barrett's esophagus (3 cm or more, long segment Barrett's esophagus \[LSBE\]), eosinophilic esophagitis, esophageal varices, scleroderma, viral or fungal infection, and esophageal stenosis; a history of radiation therapy or cryotherapy for the esophagus; or caustic or physiochemical trauma (eg, esophageal sclerotherapy). However, participants with Barrett's mucosa (less than 3 cm, short segment Barrett's esophagus \[SSBE\]) or Schatzki's ring (a mucosal tissue ring lining the inferior esophageal sphincter) are permitted to participate. 7. The participant has a history of surgery or treatment affecting gastroesophageal reflux, including fundoplication and mechanical dilatation for esophageal stenosis (except Schatzki's ring), or a history of gastric or duodenal surgery (except endoscopic removal of benign polyps). 8. The participant has acute upper gastrointestinal bleeding or gastric or duodenal ulcer, characterized by a defective mucosa with white coating, within 30 days prior to the start of the run-in period (Visit 1). However, participants with gastric or duodenal erosion are permitted to participate. 9. The participant has acute gastritis or acute exacerbation of chronic gastritis. 10. The participant has, or has a history of, Zollinger-Ellison syndrome or gastric acid hypersecretion disorders. 11. The participant has, or has a history of chest pain due to cardiac disease, or has chest pain suspectedly caused by cardiac disease within 1 year prior to the start of the run-in period (Visit 1). 12. The participant has any other concurrent upper gastrointestinal symptoms more severe than heartburn. 13. The participant has depression. 14. The participant has, has a history of, or is suspected of functional upper gastrointestinal disorders, such as functional dyspepsia and functional heartburn diagnosed by the Rome IV criteria. 15. The participant has a history of hypersensitivity or allergies to TAK-438 (including the formulation excipients). 16. The participant has a history or complication of drug abuse (defined as any illicit drug use) or of alcohol abuse within 1 years prior to the start of the run-in period (Visit 1). 17. The participant requires any excluded medications or treatments. 18. The female participant who is pregnant, is lactating, or is intending to become pregnant or to donate ova any time between the informed consent signing and 4 weeks after the last dose of study drug. 19. The participant has any serious neurological, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, endocrinological, or hematologic diseases. 20. The participant needs surgery requiring hospitalization during the course of the study, or surgery requiring hospitalization is scheduled for the participant during the course of the study. 21. The participant has a history of malignancy or is treated for malignancy within 5 years prior to the start of the run-in period (Visit 1). However, participants who have recovered completely from cutaneous basal cell carcinoma or from cervical carcinoma in situ are permitted to participate. 22. The participant has acquired immunodeficiency syndrome (AIDS) or hepatitis, is a human immunodeficiency virus (HIV) carrier, or tested positive for the hepatitis B virus surface antigen (HBsAg) or the hepatitis C virus (HCV) antibody. However, participants who tested negative for HCV antigen or HCV-RNA are permitted to participate. 23. The participant has any of the following abnormal clinical laboratory test values at the start of the run-in period (Visit 1): * Creatinine \> 2 mg/dL. * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> upper limit of normal (ULN). * Bilirubin (Total bilirubin) \> ULN.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Days Without Symptoms of Heartburn | Up to Week 4 | Heartburn symptoms were collected by participant diaries. Participants recorded the presence and severity (Without symptom \[No symptom: 0, No hindrance to daily activities: 1\], With symptom \[Mild: 2, Moderate: 3, Severe: 4\]) of heartburn in a daily participant diary. The score range was 0-4, with the higher scores reflecting the greater severity. Reported data was the percentage of days for each group, calculated by the number of days without heartburn divided by the number of days of treatment period. |
| Cumulative Rate of Improvement in Symptoms of Heartburn | Day 0 to Day 24 | Heartburn symptoms were collected by participant diaries. Participants recorded the presence and severity (Without symptom \[No symptom: 0, No hindrance to daily activities: 1\], With symptom \[Mild: 2, Moderate: 3, Severe: 4\]) of heartburn in a daily participant diary. The score range was 0-4, with the higher scores reflecting the greater severity. Cumulative rate of improvement was calculated as percentage of participants who experienced symptom improvement. Symptom improvement was defined as symptoms experienced on less than 2 days of the last 7 days. The cumulative data was collected between Day 0 and Day 24 and is reported for the following time points: Days 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24. Data not collected were shown as NA = Not Applicable. |
| Severity of Symptoms of Heartburn | Up to Week 4 | Participants recorded the presence and severity (Without symptom \[No symptom: 0, No hindrance to daily activities: 1\], With symptom \[Mild: 2, Moderate: 3, Severe: 4\]) of heartburn in a daily participant diary. The score range was 0-4, with the higher scores reflecting the greater severity. The severity of heartburn was calculated by the number of severity score in daily diaries. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 0 to Day 24 | Participants recorded presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe:4\]) of heartburn in daily participant diary. The score range was 0-4, with higher scores reflecting the greater severity. Cumulative rate of improvement calculated as percentage of participants who experienced symptom improvement. Response evaluated per Criteria 2, i.e. Improved: proportion of days participant experienced heartburn during treatment period up to Week 2 \[Day 14\] was lower than that during run-in period; Not improved: proportion of days participants experienced heartburn during treatment period up to Week 2 \[Day 14\] was equal to or larger than that during the run-in period. Cumulative data was collected between Day 0 and Day 24 and is reported for following time points: Days 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24. Data not collected were shown as NA=Not Applicable. |
| Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 0 to Day 24 | Participants recorded presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe:4\]) of heartburn in daily participant diary. The score range was 0-4, with higher scores reflecting the greater severity. Cumulative rate of improvement calculated as percentage of participants who experienced symptom improvement. The response evaluated per Criteria 2, i.e. Improved: proportion of days participant experienced heartburn during treatment period up to Week 2 \[Day 14\] was lower than that during run-in period; Not improved: proportion of days participants experienced heartburn during treatment period up to Week 2 \[Day 14\] was equal to or larger than that during run-in period. Cumulative data was collected between Day 0 and Day 24 and is reported for following time points: Days 0, 5, 9, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24. Data not collected shown as NA=Not Applicable. |
| Severity of Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) at Week 2 | Up to Week 4 | Participants recorded the presence and severity (Without symptom \[No symptom: 0, No hindrance to daily activities: 1\], With symptom \[Mild: 2, Moderate: 3, Severe: 4\]) of heartburn in a daily participant diary. The score range was 0-4, the higher scores indicates greater severity. The severity was calculated in each subgroup of response (improved or not improved) according to Criteria 1, i.e. Improved: participants experienced heartburn on less than 2 days of the 7 days prior to Week 2 \[Day 8 through Day 14\]; Not improved: participants experienced heartburn on 2 days or more of the 7 days prior to Week 2 \[Day 8 through Day 14\] and Criteria 2, i.e. Improved: proportion of days the participants experienced heartburn during the treatment period up to Week 2 \[Day 14\] was lower than that during the run-in period; Not improved: proportion of days the participants experienced heartburn during the treatment period up to Week 2 \[Day 14\] was equal to or larger than that during the run-in period. |
| Percentage of Days Without Symptoms of Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N or M) at Baseline | Up to Week 4 | Heartburn symptoms were collected by participant diaries. Participants recorded the presence and severity (Without symptom \[No symptom: 0, No hindrance to daily activities: 1\], With symptom \[Mild: 2, Moderate: 3, Severe: 4\]) of heartburn in a daily participant diary. The score range was 0-4, higher scores indicates greater severity. The percentage was calculated in each subgroup of the endoscopic findings where Grade N: normal mucosa; Grade M: minimal changes to the mucosa, such as erythema and/or whitish turbidity; Grade A: non-confluent mucosal breaks \<5mm in length; Grade B: non-confluent mucosal breaks ≥5mm in length; Grade C: confluent mucosal breaks \<75% circumferential; Grade D: confluent mucosal breaks \>75% circumferential. |
| Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 0 to Day 24 | Participants recorded presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe:4\]) of heartburn in participant diary. The score range was 0-4, higher scores indicates greater severity. Cumulative rate of improvement calculated as percentage of participants who experienced symptom improvement. Cumulative rate calculated in subgroup of Grade N per modified LA classification. Modified LA classification Grade N: normal mucosa; Grade M: minimal changes to mucosa; Grade A: nonconfluent mucosal breaks \<5mm in length; Grade B: non-confluent mucosal breaks ≥5mm in length; Grade C: confluent mucosal breaks \<75% circumferential; Grade D: confluent mucosal breaks \>75% circumferential. Cumulative data collected between Day 0 and 24 and reported for time points: Days 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24. Data not collected shown as NA=Not Applicable. |
| Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 0 to Day 24 | Participants recorded presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe:4\]) of heartburn in participant diary. Score range was 0-4, higher scores indicates greater severity. Cumulative rate of improvement calculated as percentage of participants who experienced symptom improvement. Cumulative rate calculated in subgroup of Grade M per modified LA classification. Modified LA classification Grade N: normal mucosa; Grade M: minimal changes to mucosa; Grade A: nonconfluent mucosal breaks \<5mm in length; Grade B: non-confluent mucosal breaks ≥5mm in length; Grade C: confluent mucosal breaks \<75% circumferential; Grade D: confluent mucosal breaks \>75% circumferential. Cumulative data collected between Day 0 and 24 and reported for time points: Days 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24. Data not collected shown as NA=Not Applicable. |
| Severity of Symptoms of Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N or M) at Baseline | Up to Week 4 | Heartburn symptoms were collected by participant diaries. Participants recorded the presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe:4\]) of heartburn in a daily participant diary. The score range was 0-4, with the higher scores reflecting the greater severity. The severity of heartburn was calculated in each subgroup of the endoscopic findings where Grade N: normal mucosa; Grade M: minimal changes to the mucosa, such as erythema and/or whitish turbidity; Grade A: non-confluent mucosal breaks \<5mm in length; Grade B: non-confluent mucosal breaks ≥5mm in length; Grade C: confluent mucosal breaks \<75% circumferential; Grade D: confluent mucosal breaks \>75% circumferential. |
| Percentage of Days Without Symptoms of Heartburn Stratified by Subgroup of Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Up to Week 4 | Heartburn symptoms were collected by participant diaries. Participants recorded the presence and severity (Without symptom \[No symptom: 0, No hindrance to daily activities: 1\], With symptom \[Mild: 2, Moderate: 3, Severe: 4\]) of heartburn in a daily participant diary. The score range was 0-4, higher scores indicates greater severity. The percentage was calculated in each subgroup (response; Grade N and improved, response; Grade N and not improved, response; Grade M and improved, response; Grade M and not improved) according to Criteria 1 and 2. The modified LA classification Grade N indicates the participants with normal mucosa and Grade M indicates the participants with minimal changes to the mucosa. |
| Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 0 to Day 22 | Participants recorded the presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe:4\]) of heartburn in participant diary. Score range was 0-4, higher scores indicates greater severity. Cumulative rate of improvement calculated as percentage of participants who experienced symptom improvement. Response was evaluated per Criteria 1, i.e. Improved: participants experienced heartburn on less than 2 days of 7 days prior to Week 2 \[Day 8 through Day 14\]; Not improved: participants experienced heartburn on 2 days or more of the 7 days prior to Week 2 \[Day 8 through Day 14\]. Modified LA classification Grade N: normal mucosa and Grade M: minimal changes to the mucosa. Cumulative data was collected between Day 0 and Day 22 and is reported for following time points: Days 0, 1, 2, 3, 4, 5, 6, 7, 8, 11, 19, 20, and 22. Data not collected were shown as NA=Not Applicable. |
| Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 0 to Day 24 | Participants recorded presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe:4\]) of heartburn in participant diary. Score range was 0-4, higher scores indicates greater severity. Cumulative rate of improvement calculated as percentage of participants who experienced symptom improvement. Response was evaluated per Criteria 1, i.e. Improved: participants experienced heartburn on less than 2 days of 7 days prior to Week 2 \[Day 8 through Day 14\]; Not improved: participants experienced heartburn on 2 days or more of 7 days prior to Week 2 \[Day 8 through Day 14\]. Modified LA classification Grade N indicates participants with normal mucosa and Grade M indicates participants with minimal changes to mucosa). Cumulative data was collected between Day 0 and Day 22 and is reported for following time points: Days 0, 9, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 and 22. Data not collected were shown as NA=Not Applicable. |
| Percentage of Days Without Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) at Week 2 | Up to Week 4 | Participants recorded the presence and severity of heartburn in a daily participant diary. Percentage of days without heartburn was calculated in each subgroup of the response (improved or not improved) according to Criteria 1, i.e. Improved: the participants experienced heartburn on less than 2 days of the 7 days prior to Week 2 \[Day 8 through Day 14\]; Not improved: the participants experienced heartburn on 2 days or more of the 7 days prior to Week 2 \[Day 8 through Day 14\] and Criteria 2, i.e. Improved: the proportion of days the participants experienced heartburn during the treatment period up to Week 2 \[Day 14\] was lower than that during the run-in period; Not improved: the proportion of days the participants experienced heartburn during the treatment period up to Week 2 \[Day 14\] was equal to or larger than that during the run-in period. |
| Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 0 to Day 24 | Participants recorded presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe:4\]) of heartburn in a daily participant diary. Score range was 0-4, higher score indicates greater severity. Cumulative rate of improvement calculated as percentage of participants who experienced symptom improvement. Response evaluated per Criteria 1, i.e. Improved: participants experienced heartburn on \< 2 days of the 7 days prior to Week 2 \[Day 8 to 14\]; Not improved: participants experienced heartburn on \>= 2 days of 7 days prior to Week 2 \[Day 8 to 14\]. Modified LA classification Grade N indicates participants with normal mucosa and Grade M indicates participants with minimal changes to mucosa). Cumulative data collected between Day 0 and 24 and reported for following time points: Days 0, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24. Data not collected were shown as NA=Not Applicable. |
| Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 0 to Day 22 | Participants recorded presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe:4\]) of heartburn in participant diary. Score range was 0-4, higher score indicates greater severity. Cumulative rate of improvement calculated as percentage of participants who experienced symptom improvement. Response was evaluated per Criteria 2, i.e. Improved: participants experienced heartburn during treatment period up to Week 2 \[Day 14\] was lower than during run-in period; Not improved: participants experienced heartburn during treatment period up to Week 2 \[Day 14\] was equal to or larger than during run-in period. Modified LA classification Grade N: normal mucosa and Grade M: minimal changes to mucosa). Cumulative data collected between Day 0 and 22 and reported for following time points: Days 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, and 22. Data not collected shown as NA=Not Applicable. |
| Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 0 to Day 24 | Participants recorded presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe:4\]) of heartburn in participant diary. Score range was 0-4, higher score indicates greater severity. Cumulative rate of improvement was calculated as percentage of participants who experienced symptom improvement. Response was evaluated per Criteria 2, i.e. Improved: participants experienced heartburn during treatment period up to Week 2 \[Day 14\] was lower than during run-in period; Not improved: participants experienced heartburn during treatment period up to Week 2 \[Day 14\] was equal to or larger than during run-in period. Modified LA classification Grade N: normal mucosa and Grade M: minimal changes to mucosa. Cumulative data was collected between Day 0 and Day 24 and is reported for following time points: Days 0, 5, 9, 11, 12, 13, 14, 19, 20, 21, 22, 23, and 24. Data not collected were shown as NA=Not Applicable. |
| Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 0 to Day 24 | Participants recorded presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe:4\]) of heartburn in participant diary. Score range was 0-4, higher score indicates greater severity. Cumulative rate of improvement calculated as percentage of participants who experienced symptom improvement. Response was evaluated per Criteria 2, i.e. Improved: participants experienced heartburn during treatment period up to Week 2 \[Day 14\] was lower than during run-in period; Not improved: participants experienced heartburn during treatment period up to Week 2 \[Day 14\] was equal or larger than during run-in period. Modified LA classification Grade N: normal mucosa and Grade M: minimal changes to mucosa. Cumulative data collected between Day 0 and 24 and reported for following time points: Days 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24. Data not collected shown as NA=Not Applicable. |
| Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 0 to Day 23 | Participants recorded presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe: 4\]) of heartburn in participant diary. Score range was 0-4, higher score indicates greater severity. Cumulative rate of improvement calculated as percentage of participants who experienced symptom improvement. Response was evaluated per Criteria 2, i.e. Improved: participants experienced heartburn during treatment period up to Week 2 \[Day 14\] was lower than during run-in period; Not improved: participants experienced heartburn during treatment period up to Week 2 \[Day 14\] was equal to or larger than during run-in period. Modified LA classification Grade N: normal mucosa and Grade M: minimal changes to mucosa). Cumulative data was collected between Day 0 and Day 23 and is reported for following time points: Days 0, 9, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 23. Data not collected shown as NA=Not Applicable. |
| Severity of Symptoms of Heartburn in Subgroup Stratified by Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Up to Week 4 | Heartburn symptoms were collected by participant diaries. Participants recorded the presence and severity (Without symptom \[No symptom: 0, No hindrance to daily activities: 1\], With symptom \[Mild: 2, Moderate: 3, Severe: 4\]) of heartburn in a daily participant diary. The score range was 0-4, with the higher scores reflecting the greater severity. The mean severity of heartburn was calculated in each subgroup (response; Grade N and improved, response; Grade N and not improved, response; Grade M and improved, response; Grade M and not improved) according to criteria 1 and 2. The modified LA classification Grade N indicates the participants with normal mucosa and Grade M indicates the participants with minimal changes to the mucosa. |
| Percentage of Days Without Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) to Acid Suppressants in Participants Who Had a Medication History | Up to Week 4 | Heartburn symptoms were collected by participant diaries. Participants recorded the presence and severity (Without symptom \[No symptom: 0, No hindrance to daily activities: 1\], With symptom \[Mild: 2, Moderate: 3, Severe: 4\]) of heartburn in a daily participant diary. The score range was 0-4, higher score indicates greater severity. The percentage was calculated in each subgroup of the response (improved or not improved) in the participants who had a medication history of any of acid suppressants. The acid suppressants include proton pump inhibitors \[PPIs\], histamine H2-receptor antagonists \[H2RAs\], or other agents \[anticholinergics or anti-gastrin drugs\]. |
| Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Up to Week 4 | Participants recorded presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe:4\]) of heartburn in participant diary. Score range was 0-4, higher score indicates greater severity. Cumulative rate of improvement calculated as percentage of participants who experienced symptom improvement. Cumulative improvement rate calculated in each subgroup of the response (improved or not improved) in participants who had medication history of any of acid suppressants. Acid suppressants include proton pump inhibitors \[PPIs\], histamine H2-receptor antagonists \[H2RAs\], or other agents \[anticholinergics or anti-gastrin drugs\]. Cumulative data collected between Day 0 and Day 23 and is reported for following time points: Days 0, 1, 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 and 23. Data not collected were shown as NA=Not Applicable. |
| Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved) to Acid Suppressants in Participants Who Had a Medication History | Up to Week 4 | Participants recorded presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe:4\]) of heartburn in participant diary. Score range was 0-4, higher score indicates greater severity. Cumulative rate of improvement calculated as percentage of participants who experienced symptom improvement. Cumulative improvement rate calculated in each subgroup of the response (improved or not improved) in participants who had medication history of any of acid suppressants. Acid suppressants include proton pump inhibitors \[PPIs\], histamine H2-receptor antagonists \[H2RAs\], or other agents \[anticholinergics or anti-gastrin drugs\]. Cumulative data was collected between Day 0 and Day 23 and is reported for following time points: Days 0, 1, 5, 9, 16, 19, and 20. Data not collected were shown as NA=Not Applicable. |
| Severity of Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) to Acid Suppressants in Participants Who Had a Medication History | Up to Week 4 | Heartburn symptoms were collected by participant diaries. Participants recorded the presence and severity (Without symptom \[No symptom: 0, No hindrance to daily activities: 1\], With symptom \[Mild: 2, Moderate: 3, Severe: 4\]) of heartburn in a daily participant diary. The score range was 0-4, with the higher scores reflecting the greater severity. The mean severity of heartburn was calculated in each subgroup of the response (improved or not improved) in the participants who had a medication history of any of acid suppressants. The acid suppressants include proton pump inhibitors \[PPIs\], histamine H2-receptor antagonists \[H2RAs\], or other agents \[anticholinergics or anti-gastrin drugs\]. |
| Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 0 to Day 22 | Participants recorded presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe:4\]) of heartburn in participant diary. Score range was 0-4, higher score indicates greater severity. Cumulative rate of improvement calculated as percentage of participants who experienced symptom improvement. Response was evaluated per Criteria 1, i.e. Improved: participants experienced heartburn on less than 2 days of 7 days prior to Week 2 \[Day 8 through Day 14\]; Not improved: participants experienced heartburn on 2 days or more of 7 days prior to Week 2 \[Day 8 through Day 14\]. Modified LA classification Grade N indicates participants with normal mucosa and Grade M indicates participants with minimal changes to mucosa). Cumulative data collected between Day 0 and Day 22 and is reported for following time points: Days 0, 1, 2, 3, 4, 5, 6, 7, 8, 11, 15, 16, 17, 18, 20, 21 and 22. Data not collected were shown as NA=Not Applicable. |
| Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 0 to Day 22 | Participants recorded presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe:4\]) of heartburn in daily participant diary. The score range was 0-4, with the higher scores reflecting the greater severity. Cumulative rate of improvement was calculated as percentage of participants who experienced symptom improvement. The response was evaluated per Criteria 1, i.e. Improved: the participants experienced heartburn on less than 2 days of the 7 days prior to Week 2 \[Day 8 through Day 14\]; Not improved: the participants experienced heartburn on 2 days or more of the 7 days prior to Week 2 \[Day 8 through Day 14\]. Cumulative data was collected between Day 0 and Day 22 and is reported for following time points: Days 0, 1, 2, 3, 4, 5, 6, 7, 8, 11, 15, 16, 17, 18, 19, 20, 21, and 22. Data not collected were shown as NA = Not Applicable. |
| Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 0 to Day 24 | Participants recorded presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe:4\]) of heartburn in daily participant diary. The score range was 0-4, with the higher scores reflecting the greater severity. Cumulative rate of improvement is calculated as percentage of participants who experienced symptom improvement. The response was evaluated per Criteria 1, i.e. Improved: the participants experienced heartburn on less than 2 days of the 7 days prior to Week 2 \[Day 8 through Day 14\]; Not improved: the participants experienced heartburn on 2 days or more of the 7 days prior to Week 2 \[Day 8 through Day 14\]. Cumulative data was collected between Day 0 and Day 24 and is reported for following time points: Days 0, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24. Data not collected were shown as NA = Not Applicable. |
Countries
Japan
Participant flow
Recruitment details
Participants took part in the study at 44 investigative sites in Japan from 15 November 2016 to 26 February 2018.
Pre-assignment details
Participants with a diagnosis of non-erosive gastroesophageal reflux disease (NERD) were enrolled and received one tablet of placebo orally, once daily in a run-in period. After that, the participants who met all the entry criteria were randomized in 1:1 ratio to receive TAK-438 10 mg or TAK-438 placebo-matching tablets.
Participants by arm
| Arm | Count |
|---|---|
| Placebo TAK-438 placebo-matching tablets, orally, once daily after breakfast for 1 week in run-in period followed by TAK-438 placebo-matching tablets, orally, once daily after breakfast for up to 4 weeks in treatment period. | 245 |
| TAK-438 10 mg TAK-438 placebo-matching tablets, orally, once daily after breakfast for 1 week in run-in period followed by TAK-438 10 mg tablets, orally, once daily after breakfast for up to 4 weeks in treatment period. | 239 |
| Total | 484 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 |
| Overall Study | Randomized but Not Treated | 0 | 1 |
| Overall Study | Withdrawal by Participant | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | TAK-438 10 mg |
|---|---|---|---|
| Age, Continuous | 51.8 years STANDARD_DEVIATION 15.38 | 52.3 years STANDARD_DEVIATION 14.88 | 52.8 years STANDARD_DEVIATION 14.37 |
| Barrett's Mucosa No | 189 Participants | 377 Participants | 188 Participants |
| Barrett's Mucosa Yes (Less than 3 cm) | 56 Participants | 107 Participants | 51 Participants |
| Body Mass Index (BMI) | 22.67 kg/m^2 STANDARD_DEVIATION 3.431 | 22.69 kg/m^2 STANDARD_DEVIATION 3.4 | 22.71 kg/m^2 STANDARD_DEVIATION 3.375 |
| Consumption of Alcohol Drank a Couple of Days Per Month | 54 Participants | 108 Participants | 54 Participants |
| Consumption of Alcohol Drank a Couple of Days Per Week | 62 Participants | 125 Participants | 63 Participants |
| Consumption of Alcohol Drank Every Day | 59 Participants | 105 Participants | 46 Participants |
| Consumption of Alcohol Never Drank | 70 Participants | 146 Participants | 76 Participants |
| Consumption of Caffeine Had Caffeine Consumption | 192 Participants | 382 Participants | 190 Participants |
| Consumption of Caffeine Had No Caffeine Consumption | 53 Participants | 102 Participants | 49 Participants |
| Endoscopic Findings by Central Adjudication Committee (CAC) Grade M | 168 Participants | 325 Participants | 157 Participants |
| Endoscopic Findings by Central Adjudication Committee (CAC) Grade N | 77 Participants | 159 Participants | 82 Participants |
| Endoscopic Findings by Principal Investigator (PI) Grade M | 163 Participants | 321 Participants | 158 Participants |
| Endoscopic Findings by Principal Investigator (PI) Grade N | 82 Participants | 163 Participants | 81 Participants |
| Esophageal Hiatal Hernia No | 146 Participants | 282 Participants | 136 Participants |
| Esophageal Hiatal Hernia Yes (2 cm or More) | 17 Participants | 35 Participants | 18 Participants |
| Esophageal Hiatal Hernia Yes (Less than 2 cm) | 82 Participants | 167 Participants | 85 Participants |
| Factors and Improvement: Above Factors are NA or cannot be Specified No | 241 Participants | 472 Participants | 231 Participants |
| Factors and Improvement: Above Factors are NA or cannot be Specified Yes | 4 Participants | 12 Participants | 8 Participants |
| Factors and Improvement: Diet, Acidic Foods (Citrus Fruits, Carb. Beverage) No | 166 Participants | 339 Participants | 173 Participants |
| Factors and Improvement: Diet, Acidic Foods (Citrus Fruits, Carb. Beverage) Yes | 79 Participants | 145 Participants | 66 Participants |
| Factors and Improvement: Diet, Carbohydrates (Grains, Potatoes, etc.) No | 130 Participants | 279 Participants | 149 Participants |
| Factors and Improvement: Diet, Carbohydrates (Grains, Potatoes, etc.) Yes | 115 Participants | 205 Participants | 90 Participants |
| Factors and Improvement: Diet, Fatty Foods (Fried Foods, Stodge, etc.) No | 80 Participants | 163 Participants | 83 Participants |
| Factors and Improvement: Diet, Fatty Foods (Fried Foods, Stodge, etc.) Yes | 165 Participants | 321 Participants | 156 Participants |
| Factors and Improvement: Diet, Other No | 240 Participants | 466 Participants | 226 Participants |
| Factors and Improvement: Diet, Other Yes | 5 Participants | 18 Participants | 13 Participants |
| Factors and Improvement: Diet, Spices (Pepper, Curry, etc.) No | 162 Participants | 324 Participants | 162 Participants |
| Factors and Improvement: Diet, Spices (Pepper, Curry, etc.) Yes | 83 Participants | 160 Participants | 77 Participants |
| Factors and Improvement: Diet, Sweet Foods (Chocolate, etc.) No | 158 Participants | 319 Participants | 161 Participants |
| Factors and Improvement: Diet, Sweet Foods (Chocolate, etc.) Yes | 87 Participants | 165 Participants | 78 Participants |
| Factors and Improvement: Habits, Caffeine Ingestion No | 133 Participants | 260 Participants | 127 Participants |
| Factors and Improvement: Habits, Caffeine Ingestion Yes | 112 Participants | 224 Participants | 112 Participants |
| Factors and Improvement: Habits, Drinking Alcohol No | 166 Participants | 337 Participants | 171 Participants |
| Factors and Improvement: Habits, Drinking Alcohol Yes | 79 Participants | 147 Participants | 68 Participants |
| Factors and Improvement: Habits, Smoking No | 216 Participants | 436 Participants | 220 Participants |
| Factors and Improvement: Habits, Smoking Yes | 29 Participants | 48 Participants | 19 Participants |
| Factors and Improvement: Improving Lifestyle No | 161 Participants | 303 Participants | 142 Participants |
| Factors and Improvement: Improving Lifestyle Yes | 84 Participants | 181 Participants | 97 Participants |
| Factors and Improvement: Movement, Forward Flexion No | 140 Participants | 296 Participants | 156 Participants |
| Factors and Improvement: Movement, Forward Flexion Yes | 105 Participants | 188 Participants | 83 Participants |
| Factors and Improvement: Movement, Lying in Bed No | 146 Participants | 296 Participants | 150 Participants |
| Factors and Improvement: Movement, Lying in Bed Yes | 99 Participants | 188 Participants | 89 Participants |
| Factors and Improvement: Movement, Other No | 232 Participants | 459 Participants | 227 Participants |
| Factors and Improvement: Movement, Other Yes | 13 Participants | 25 Participants | 12 Participants |
| Factors and Improvement: Physical Factors, Evident Obesity No | 231 Participants | 455 Participants | 224 Participants |
| Factors and Improvement: Physical Factors, Evident Obesity Yes | 14 Participants | 29 Participants | 15 Participants |
| Factors and Improvement: Physical Factors, Kyphosis No | 241 Participants | 472 Participants | 231 Participants |
| Factors and Improvement: Physical Factors, Kyphosis Yes | 4 Participants | 12 Participants | 8 Participants |
| Gastrin | 91.6 pg/mL STANDARD_DEVIATION 53.29 | 97.3 pg/mL STANDARD_DEVIATION 133.83 | 103.1 pg/mL STANDARD_DEVIATION 182.68 |
| Height | 161.7 cm STANDARD_DEVIATION 8.62 | 161.1 cm STANDARD_DEVIATION 8.97 | 160.5 cm STANDARD_DEVIATION 9.29 |
| History of H. pylori Eradication More than One Year Before | 58 Participants | 107 Participants | 49 Participants |
| History of H. pylori Eradication No | 185 Participants | 374 Participants | 189 Participants |
| History of H. pylori Eradication Within the Last Year | 2 Participants | 3 Participants | 1 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Ratio of Pepsinogen I to Pepsinogen II | 7.63 ratio STANDARD_DEVIATION 2.722 | 7.60 ratio STANDARD_DEVIATION 2.585 | 7.57 ratio STANDARD_DEVIATION 2.442 |
| Region of Enrollment Japan | 245 Participants | 484 Participants | 239 Participants |
| Response to Acid Suppressants Heartburn has been Resolved | 31 Participants | 76 Participants | 45 Participants |
| Response to Acid Suppressants Heartburn has not been Resolved but Relieved | 52 Participants | 95 Participants | 43 Participants |
| Response to Acid Suppressants Heartburn has Remained Unchanged | 8 Participants | 13 Participants | 5 Participants |
| Response to Acid Suppressants Improved | 83 Participants | 171 Participants | 88 Participants |
| Response to Acid Suppressants Not Improved | 8 Participants | 13 Participants | 5 Participants |
| Serological Determination for H. pylori Negative | 208 Participants | 417 Participants | 209 Participants |
| Serological Determination for H. pylori Positive | 37 Participants | 65 Participants | 28 Participants |
| Severity of Symptoms, Heartburn | 1.641 score on a scale STANDARD_DEVIATION 0.5747 | 1.702 score on a scale STANDARD_DEVIATION 0.5986 | 1.765 score on a scale STANDARD_DEVIATION 0.6171 |
| Severity of Symptoms, Regurgitation | 1.074 score on a scale STANDARD_DEVIATION 0.8398 | 1.091 score on a scale STANDARD_DEVIATION 0.8739 | 1.109 score on a scale STANDARD_DEVIATION 0.9092 |
| Sex: Female, Male Female | 140 Participants | 301 Participants | 161 Participants |
| Sex: Female, Male Male | 105 Participants | 183 Participants | 78 Participants |
| Smoking Classification Current Smoker | 52 Participants | 96 Participants | 44 Participants |
| Smoking Classification Ex-smoker | 69 Participants | 136 Participants | 67 Participants |
| Smoking Classification Never Smoked | 124 Participants | 252 Participants | 128 Participants |
| Use of H2-Receptor Antagonists (H2RA) Within 180 Days Prior to IC No | 216 Participants | 427 Participants | 211 Participants |
| Use of H2-Receptor Antagonists (H2RA) Within 180 Days Prior to IC Yes | 29 Participants | 57 Participants | 28 Participants |
| Use of Other Agents (Anticholinergics or Anti-gastrin Drugs) within 180 Days Prior to IC No | 221 Participants | 438 Participants | 217 Participants |
| Use of Other Agents (Anticholinergics or Anti-gastrin Drugs) within 180 Days Prior to IC Yes | 24 Participants | 46 Participants | 22 Participants |
| Use of Proton Pump Inhibitors (PPIs) Within 180 Days Prior to Informed Consent (IC) No | 200 Participants | 384 Participants | 184 Participants |
| Use of Proton Pump Inhibitors (PPIs) Within 180 Days Prior to Informed Consent (IC) Yes | 45 Participants | 100 Participants | 55 Participants |
| Weight | 59.6 kg STANDARD_DEVIATION 12.04 | 59.2 kg STANDARD_DEVIATION 11.61 | 58.7 kg STANDARD_DEVIATION 11.15 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 245 | 0 / 238 |
| other Total, other adverse events | 12 / 245 | 10 / 238 |
| serious Total, serious adverse events | 1 / 245 | 0 / 238 |
Outcome results
Primary
Cumulative Rate of Improvement in Symptoms of Heartburn
Heartburn symptoms were collected by participant diaries. Participants recorded the presence and severity (Without symptom \[No symptom: 0, No hindrance to daily activities: 1\], With symptom \[Mild: 2, Moderate: 3, Severe: 4\]) of heartburn in a daily participant diary. The score range was 0-4, with the higher scores reflecting the greater severity. Cumulative rate of improvement was calculated as percentage of participants who experienced symptom improvement. Symptom improvement was defined as symptoms experienced on less than 2 days of the last 7 days. The cumulative data was collected between Day 0 and Day 24 and is reported for the following time points: Days 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24. Data not collected were shown as NA = Not Applicable.
Time frame: Day 0 to Day 24
Population: FAS included participants who were randomized and received at least one dose of the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 2 | 15.9 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 13 | 29.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 7 | 20.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 14 | 30.6 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 4 | 17.6 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 15 | 31.4 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 8 | 21.2 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 16 | 34.3 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 1 | 14.7 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 17 | 36.3 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 9 | 23.7 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 18 | 38.4 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 5 | 18.8 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 19 | 40.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 10 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 20 | 42.7 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 3 | 16.3 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 21 | 44.7 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 11 | 25.7 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 22 | 48.6 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 6 | 19.2 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 23 | 51.3 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 12 | 27.3 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 24 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 0 | 0.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 24 | 71.3 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 0 | 0.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 1 | 23.1 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 2 | 24.4 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 3 | 25.2 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 4 | 26.1 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 5 | 28.2 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 6 | 30.4 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 7 | 32.5 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 8 | 32.9 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 9 | 34.2 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 10 | 35.5 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 11 | 38.5 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 12 | 41.1 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 13 | 44.6 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 14 | 46.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 15 | 48.9 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 16 | 49.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 17 | 51.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 18 | 54.4 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 19 | 55.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 20 | 59.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 21 | 59.5 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 22 | 62.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn | Day 23 | 66.1 percentage of participants |
p-value: 0.0003Log Rank
Primary
Percentage of Days Without Symptoms of Heartburn
Heartburn symptoms were collected by participant diaries. Participants recorded the presence and severity (Without symptom \[No symptom: 0, No hindrance to daily activities: 1\], With symptom \[Mild: 2, Moderate: 3, Severe: 4\]) of heartburn in a daily participant diary. The score range was 0-4, with the higher scores reflecting the greater severity. Reported data was the percentage of days for each group, calculated by the number of days without heartburn divided by the number of days of treatment period.
Time frame: Up to Week 4
Population: Full analysis set (FAS) included participants who were randomized and received at least one dose of the study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percentage of Days Without Symptoms of Heartburn | 61.50 percentage of days |
| TAK-438 10 mg | Percentage of Days Without Symptoms of Heartburn | 72.55 percentage of days |
p-value: 0.064395% CI: [0, 10.6]Wilcoxon Rank-Sum Test
Primary
Severity of Symptoms of Heartburn
Participants recorded the presence and severity (Without symptom \[No symptom: 0, No hindrance to daily activities: 1\], With symptom \[Mild: 2, Moderate: 3, Severe: 4\]) of heartburn in a daily participant diary. The score range was 0-4, with the higher scores reflecting the greater severity. The severity of heartburn was calculated by the number of severity score in daily diaries.
Time frame: Up to Week 4
Population: FAS included participants who were randomized and received at least one dose of the study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Severity of Symptoms of Heartburn | 1.140 score on a scale |
| TAK-438 10 mg | Severity of Symptoms of Heartburn | 1.070 score on a scale |
p-value: 0.082695% CI: [-0.24, 0.01]Wilcoxon Rank-Sum Test
Secondary
Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline
Participants recorded presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe:4\]) of heartburn in participant diary. Score range was 0-4, higher scores indicates greater severity. Cumulative rate of improvement calculated as percentage of participants who experienced symptom improvement. Cumulative rate calculated in subgroup of Grade M per modified LA classification. Modified LA classification Grade N: normal mucosa; Grade M: minimal changes to mucosa; Grade A: nonconfluent mucosal breaks \<5mm in length; Grade B: non-confluent mucosal breaks ≥5mm in length; Grade C: confluent mucosal breaks \<75% circumferential; Grade D: confluent mucosal breaks \>75% circumferential. Cumulative data collected between Day 0 and 24 and reported for time points: Days 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24. Data not collected shown as NA=Not Applicable.
Time frame: Day 0 to Day 24
Population: FAS included participants who were randomized and received at least one dose of the study drug. Number analyzed is the number of participants who were evaluable at each category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 0 | 0.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 1 | 12.9 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 2 | 14.7 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 3 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 5 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 9 | 20.9 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 14 | 27.6 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 7 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 8 | 17.8 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 10 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 11 | 21.5 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 12 | 22.7 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 13 | 25.2 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 15 | 28.8 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 16 | 31.9 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 17 | 34.4 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 18 | 35.6 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 19 | 36.9 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 20 | 40.3 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 21 | 42.6 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 22 | 47.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 23 | 50.8 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 4 | 16.6 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 24 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 6 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 23 | 59.6 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 0 | 0.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 13 | 41.2 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 1 | 23.6 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 14 | 42.5 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 2 | 24.9 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 3 | 25.5 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 4 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 21 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 5 | 27.5 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 16 | 45.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 10 | 32.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 6 | 29.4 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 15 | 44.4 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 20 | 55.1 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 17 | 47.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 7 | 30.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 22 | 57.1 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 8 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 9 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 18 | 51.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 24 | 63.3 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 11 | 35.9 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 19 | 51.6 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade M) at Baseline | Day 12 | 37.9 percentage of participants |
p-value: 0.0153Log Rank
Secondary
Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline
Participants recorded presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe:4\]) of heartburn in participant diary. The score range was 0-4, higher scores indicates greater severity. Cumulative rate of improvement calculated as percentage of participants who experienced symptom improvement. Cumulative rate calculated in subgroup of Grade N per modified LA classification. Modified LA classification Grade N: normal mucosa; Grade M: minimal changes to mucosa; Grade A: nonconfluent mucosal breaks \<5mm in length; Grade B: non-confluent mucosal breaks ≥5mm in length; Grade C: confluent mucosal breaks \<75% circumferential; Grade D: confluent mucosal breaks \>75% circumferential. Cumulative data collected between Day 0 and 24 and reported for time points: Days 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24. Data not collected shown as NA=Not Applicable.
Time frame: Day 0 to Day 24
Population: FAS included participants who were randomized and received at least one dose of the study drug. Number analyzed is the number of participants who were evaluable at each category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 3 | 19.5 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 9 | 29.3 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 20 | 47.7 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 11 | 34.1 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 4 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 12 | 36.6 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 1 | 18.3 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 13 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 5 | 23.2 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 14 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 22 | 52.1 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 15 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 6 | 24.4 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 16 | 39.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 2 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 17 | 40.2 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 18 | 43.9 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 7 | 26.8 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 19 | 46.3 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 0 | 0.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 21 | 49.1 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 8 | 28.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 23 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 24 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 12 | 47.3 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 20 | 66.3 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 21 | 67.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 23 | 78.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 24 | 89.4 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 0 | 0.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 1 | 22.2 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 2 | 23.5 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 3 | 24.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 4 | 27.2 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 5 | 29.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 6 | 32.3 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 7 | 36.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 8 | 37.3 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 9 | 41.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 11 | 43.5 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 17 | 58.6 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 13 | 51.1 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 14 | 54.8 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 15 | 57.3 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 16 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 18 | 61.1 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 19 | 63.6 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N) at Baseline | Day 22 | 73.4 percentage of participants |
p-value: 0.0059Log Rank
Secondary
Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M)
Participants recorded presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe:4\]) of heartburn in participant diary. Score range was 0-4, higher score indicates greater severity. Cumulative rate of improvement calculated as percentage of participants who experienced symptom improvement. Response was evaluated per Criteria 1, i.e. Improved: participants experienced heartburn on less than 2 days of 7 days prior to Week 2 \[Day 8 through Day 14\]; Not improved: participants experienced heartburn on 2 days or more of 7 days prior to Week 2 \[Day 8 through Day 14\]. Modified LA classification Grade N indicates participants with normal mucosa and Grade M indicates participants with minimal changes to mucosa). Cumulative data collected between Day 0 and Day 22 and is reported for following time points: Days 0, 1, 2, 3, 4, 5, 6, 7, 8, 11, 15, 16, 17, 18, 20, 21 and 22. Data not collected were shown as NA=Not Applicable.
Time frame: Day 0 to Day 22
Population: FAS included participants who were randomized and received at least one dose of the study drug. Number analyzed is the number of participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 1 | 38.2 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 11 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 5 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 15 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 3 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 16 | 54.5 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 6 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 17 | 56.4 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 2 | 43.6 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 18 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 7 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 20 | 60.8 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 4 | 49.1 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 21 | 63.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 8 | 52.7 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 22 | 68.3 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 0 | 0.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 22 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 0 | 0.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 1 | 61.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 2 | 65.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 3 | 66.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 4 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 5 | 71.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 6 | 76.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 7 | 80.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 8 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 11 | 81.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 15 | 83.3 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 16 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 17 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 18 | 86.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 20 | 90.5 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 21 | NA percentage of participants |
p-value: 0.0004Log Rank
Secondary
Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N)
Participants recorded the presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe:4\]) of heartburn in participant diary. Score range was 0-4, higher scores indicates greater severity. Cumulative rate of improvement calculated as percentage of participants who experienced symptom improvement. Response was evaluated per Criteria 1, i.e. Improved: participants experienced heartburn on less than 2 days of 7 days prior to Week 2 \[Day 8 through Day 14\]; Not improved: participants experienced heartburn on 2 days or more of the 7 days prior to Week 2 \[Day 8 through Day 14\]. Modified LA classification Grade N: normal mucosa and Grade M: minimal changes to the mucosa. Cumulative data was collected between Day 0 and Day 22 and is reported for following time points: Days 0, 1, 2, 3, 4, 5, 6, 7, 8, 11, 19, 20, and 22. Data not collected were shown as NA=Not Applicable.
Time frame: Day 0 to Day 22
Population: FAS included participants who were randomized and received at least one dose of the study drug. Number analyzed is the number of participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 7 | 78.6 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 0 | 0.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 1 | 53.6 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 2 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 3 | 57.1 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 4 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 5 | 67.9 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 6 | 71.4 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 8 | 82.1 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 11 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 19 | 85.7 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 20 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 22 | 89.3 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 20 | 82.9 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 6 | 66.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 0 | 0.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 7 | 74.4 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 1 | 46.2 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 19 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 2 | 48.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 8 | 76.9 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 3 | 51.3 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 22 | 100.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 4 | 56.4 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 11 | 79.5 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 5 | 61.5 percentage of participants |
p-value: 0.997Log Rank
Secondary
Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M)
Participants recorded presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe:4\]) of heartburn in participant diary. Score range was 0-4, higher score indicates greater severity. Cumulative rate of improvement calculated as percentage of participants who experienced symptom improvement. Response was evaluated per Criteria 2, i.e. Improved: participants experienced heartburn during treatment period up to Week 2 \[Day 14\] was lower than during run-in period; Not improved: participants experienced heartburn during treatment period up to Week 2 \[Day 14\] was equal or larger than during run-in period. Modified LA classification Grade N: normal mucosa and Grade M: minimal changes to mucosa. Cumulative data collected between Day 0 and 24 and reported for following time points: Days 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24. Data not collected shown as NA=Not Applicable.
Time frame: Day 0 to Day 24
Population: FAS included participants who were randomized and received at least one dose of the study drug. Number analyzed is the number of participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 1 | 19.3 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 12 | 33.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 13 | 35.8 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 6 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 15 | 36.7 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 3 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 16 | 39.4 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 7 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 17 | 43.2 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 0 | 0.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 18 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 8 | 26.6 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 19 | 44.1 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 4 | 24.8 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 20 | 48.2 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 9 | 30.3 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 21 | 50.6 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 2 | 22.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 22 | 56.1 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 10 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 23 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 5 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 24 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 11 | 31.2 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 24 | 75.2 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 0 | 0.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 1 | 32.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 2 | 34.5 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 3 | 35.4 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 4 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 5 | 38.1 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 6 | 40.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 7 | 42.5 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 8 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 9 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 10 | 45.2 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 11 | 49.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 13 | 55.1 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 15 | 56.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 16 | 57.8 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 17 | 58.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 18 | 61.4 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 19 | 62.3 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 20 | 65.1 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 21 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 22 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 23 | 69.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 12 | 51.5 percentage of participants |
p-value: 0.0175Log Rank
Secondary
Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N)
Participants recorded presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe:4\]) of heartburn in participant diary. Score range was 0-4, higher score indicates greater severity. Cumulative rate of improvement calculated as percentage of participants who experienced symptom improvement. Response was evaluated per Criteria 2, i.e. Improved: participants experienced heartburn during treatment period up to Week 2 \[Day 14\] was lower than during run-in period; Not improved: participants experienced heartburn during treatment period up to Week 2 \[Day 14\] was equal to or larger than during run-in period. Modified LA classification Grade N: normal mucosa and Grade M: minimal changes to mucosa). Cumulative data collected between Day 0 and 22 and reported for following time points: Days 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, and 22. Data not collected shown as NA=Not Applicable.
Time frame: Day 0 to Day 22
Population: FAS included participants who were randomized and received at least one dose of the study drug. Number analyzed is the number of participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 16 | 47.5 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 2 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 3 | 27.1 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 8 | 35.6 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 18 | 54.2 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 22 | 58.1 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 1 | 25.4 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 4 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 5 | 28.8 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 6 | 30.5 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 7 | 33.9 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 9 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 11 | 40.7 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 12 | 44.1 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 13 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 14 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 15 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 0 | 0.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 17 | 49.2 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 19 | 55.9 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 20 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 21 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 7 | 47.5 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 8 | 49.2 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 19 | 73.8 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 4 | 36.1 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 16 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 9 | 52.5 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 12 | 59.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 15 | 67.2 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 11 | 55.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 21 | 79.4 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 22 | 84.5 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 0 | 0.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 17 | 68.9 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 1 | 29.5 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 2 | 31.1 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 3 | 32.8 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 13 | 62.3 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 18 | 72.1 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 5 | 39.3 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 14 | 63.9 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 6 | 42.6 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 20 | 77.5 percentage of participants |
p-value: 0.0059Log Rank
Secondary
Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M)
Participants recorded presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe:4\]) of heartburn in a daily participant diary. Score range was 0-4, higher score indicates greater severity. Cumulative rate of improvement calculated as percentage of participants who experienced symptom improvement. Response evaluated per Criteria 1, i.e. Improved: participants experienced heartburn on \< 2 days of the 7 days prior to Week 2 \[Day 8 to 14\]; Not improved: participants experienced heartburn on \>= 2 days of 7 days prior to Week 2 \[Day 8 to 14\]. Modified LA classification Grade N indicates participants with normal mucosa and Grade M indicates participants with minimal changes to mucosa). Cumulative data collected between Day 0 and 24 and reported for following time points: Days 0, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24. Data not collected were shown as NA=Not Applicable.
Time frame: Day 0 to Day 24
Population: FAS included participants who were randomized and received at least one dose of the study drug. Number analyzed is the number of participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 11 | 5.6 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 16 | 20.4 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 9 | 4.6 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 17 | 23.1 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 12 | 7.4 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 0 | 0.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 19 | 26.9 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 10 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 20 | 29.9 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 14 | 14.8 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 21 | 32.2 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 22 | 36.2 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 18 | 25.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 23 | 42.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 15 | 16.7 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 24 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 13 | 11.1 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 24 | 45.6 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 21 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 0 | 0.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 9 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 10 | 3.2 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 11 | 7.4 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 12 | 10.6 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 13 | 16.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 14 | 18.1 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 15 | 20.2 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 16 | 22.3 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 17 | 24.5 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 18 | 28.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 19 | 29.8 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 20 | 33.2 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 22 | 36.4 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 23 | 40.1 percentage of participants |
p-value: 0.7999Log Rank
Secondary
Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N)
Participants recorded presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe:4\]) of heartburn in participant diary. Score range was 0-4, higher scores indicates greater severity. Cumulative rate of improvement calculated as percentage of participants who experienced symptom improvement. Response was evaluated per Criteria 1, i.e. Improved: participants experienced heartburn on less than 2 days of 7 days prior to Week 2 \[Day 8 through Day 14\]; Not improved: participants experienced heartburn on 2 days or more of 7 days prior to Week 2 \[Day 8 through Day 14\]. Modified LA classification Grade N indicates participants with normal mucosa and Grade M indicates participants with minimal changes to mucosa). Cumulative data was collected between Day 0 and Day 22 and is reported for following time points: Days 0, 9, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 and 22. Data not collected were shown as NA=Not Applicable.
Time frame: Day 0 to Day 24
Population: FAS included participants who were randomized and received at least one dose of the study drug. Number analyzed is the number of participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 15 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 16 | 16.7 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 17 | 18.5 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 18 | 24.1 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 19 | 25.9 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 20 | 27.9 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 21 | 30.1 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 22 | 32.4 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 23 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 24 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 0 | 0.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 9 | 1.9 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 11 | 9.3 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 12 | 13.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 13 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 14 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 14 | 31.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 15 | 36.6 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 23 | 63.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 16 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 11 | 9.8 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 17 | 39.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 24 | 81.5 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 18 | 43.9 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 13 | 24.4 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 19 | 48.8 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 0 | 0.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 20 | 51.2 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 12 | 17.1 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 21 | 53.8 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 9 | 7.3 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 1) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 22 | NA percentage of participants |
p-value: 0.0125Log Rank
Secondary
Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M)
Participants recorded presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe: 4\]) of heartburn in participant diary. Score range was 0-4, higher score indicates greater severity. Cumulative rate of improvement calculated as percentage of participants who experienced symptom improvement. Response was evaluated per Criteria 2, i.e. Improved: participants experienced heartburn during treatment period up to Week 2 \[Day 14\] was lower than during run-in period; Not improved: participants experienced heartburn during treatment period up to Week 2 \[Day 14\] was equal to or larger than during run-in period. Modified LA classification Grade N: normal mucosa and Grade M: minimal changes to mucosa). Cumulative data was collected between Day 0 and Day 23 and is reported for following time points: Days 0, 9, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 23. Data not collected shown as NA=Not Applicable.
Time frame: Day 0 to Day 23
Population: FAS included participants who were randomized and received at least one dose of the study drug. Number analyzed is the number of participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 13 | 3.7 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 17 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 0 | 0.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 18 | 20.4 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 14 | 11.1 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 19 | 22.3 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 12 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 20 | 24.3 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 15 | 13.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 21 | 26.5 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 9 | 1.9 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 22 | 29.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 16 | 16.7 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 23 | 43.2 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 23 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 0 | 0.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 9 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 12 | 2.4 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 13 | 4.8 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 14 | 9.5 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 15 | 14.3 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 16 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 17 | 16.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 18 | 23.8 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 19 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 20 | 29.1 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 21 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade M) | Day 22 | 36.2 percentage of participants |
p-value: 0.7505Log Rank
Secondary
Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N)
Participants recorded presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe:4\]) of heartburn in participant diary. Score range was 0-4, higher score indicates greater severity. Cumulative rate of improvement was calculated as percentage of participants who experienced symptom improvement. Response was evaluated per Criteria 2, i.e. Improved: participants experienced heartburn during treatment period up to Week 2 \[Day 14\] was lower than during run-in period; Not improved: participants experienced heartburn during treatment period up to Week 2 \[Day 14\] was equal to or larger than during run-in period. Modified LA classification Grade N: normal mucosa and Grade M: minimal changes to mucosa. Cumulative data was collected between Day 0 and Day 24 and is reported for following time points: Days 0, 5, 9, 11, 12, 13, 14, 19, 20, 21, 22, 23, and 24. Data not collected were shown as NA=Not Applicable.
Time frame: Day 0 to Day 24
Population: FAS included participants who were randomized and received at least one dose of the study drug. Number analyzed is the number of participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 0 | 0.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 22 | 35.9 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 5 | 8.7 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 9 | 13.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 11 | 17.4 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 12 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 13 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 14 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 19 | 21.7 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 20 | 26.3 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 21 | 30.9 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 23 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 24 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 21 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 9 | 5.3 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 14 | 26.3 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 0 | 0.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 22 | 39.2 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 5 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 19 | 31.6 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 24 | 100.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 11 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 20 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 12 | 10.5 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 23 | 59.5 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Both the Response (Not Improved Per Criteria 2) at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N) | Day 13 | 15.8 percentage of participants |
p-value: 0.552Log Rank
Secondary
Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2
Participants recorded presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe:4\]) of heartburn in daily participant diary. The score range was 0-4, with the higher scores reflecting the greater severity. Cumulative rate of improvement was calculated as percentage of participants who experienced symptom improvement. The response was evaluated per Criteria 1, i.e. Improved: the participants experienced heartburn on less than 2 days of the 7 days prior to Week 2 \[Day 8 through Day 14\]; Not improved: the participants experienced heartburn on 2 days or more of the 7 days prior to Week 2 \[Day 8 through Day 14\]. Cumulative data was collected between Day 0 and Day 22 and is reported for following time points: Days 0, 1, 2, 3, 4, 5, 6, 7, 8, 11, 15, 16, 17, 18, 19, 20, 21, and 22. Data not collected were shown as NA = Not Applicable.
Time frame: Day 0 to Day 22
Population: FAS included participants who were randomized and received at least one dose of the study drug. Number analyzed is the number of participants who were evaluable at each category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 1 | 43.4 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 2 | 47.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 3 | 48.2 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 4 | 51.8 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 5 | 55.4 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 6 | 56.6 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 7 | 59.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 8 | 62.7 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 11 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 15 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 16 | 63.9 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 17 | 65.1 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 18 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 19 | 66.3 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 20 | 69.2 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 21 | 70.6 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 22 | 75.5 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 0 | 0.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 19 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 1 | 55.6 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 15 | 81.8 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 2 | 58.6 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 0 | 0.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 3 | 60.6 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 16 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 4 | 62.6 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 20 | 87.6 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 5 | 67.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 17 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 6 | 72.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 22 | 93.8 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 7 | 77.8 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 18 | 83.8 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 8 | 78.8 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 21 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2 | Day 11 | 80.8 percentage of participants |
p-value: 0.0025Log Rank
Secondary
Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2
Participants recorded presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe:4\]) of heartburn in daily participant diary. The score range was 0-4, with higher scores reflecting the greater severity. Cumulative rate of improvement calculated as percentage of participants who experienced symptom improvement. Response evaluated per Criteria 2, i.e. Improved: proportion of days participant experienced heartburn during treatment period up to Week 2 \[Day 14\] was lower than that during run-in period; Not improved: proportion of days participants experienced heartburn during treatment period up to Week 2 \[Day 14\] was equal to or larger than that during the run-in period. Cumulative data was collected between Day 0 and Day 24 and is reported for following time points: Days 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24. Data not collected were shown as NA=Not Applicable.
Time frame: Day 0 to Day 24
Population: FAS included participants who were randomized and received at least one dose of the study drug. Number analyzed is the number of participants who were evaluable at each category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 6 | 26.8 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 13 | 38.7 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 3 | 23.8 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 14 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 7 | 28.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 15 | 39.3 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 0 | 0.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 16 | 42.3 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 4 | 25.6 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 17 | 45.3 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 9 | 32.1 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 18 | 47.1 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 2 | 23.2 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 19 | 48.3 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 10 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 20 | 50.9 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 5 | 26.2 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 21 | 52.4 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 11 | 34.5 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 22 | 56.7 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 1 | 21.4 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 23 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 12 | 36.9 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 24 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 8 | 29.8 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 24 | 78.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 0 | 0.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 1 | 31.6 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 2 | 33.3 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 3 | 34.5 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 4 | 35.6 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 5 | 38.5 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 6 | 41.4 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 7 | 44.3 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 8 | 44.9 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 9 | 46.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 10 | 47.8 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 11 | 51.8 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 12 | 54.1 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 13 | 57.6 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 14 | 58.2 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 15 | 60.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 16 | 61.1 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 17 | 62.3 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 18 | 65.2 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 19 | 66.3 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 20 | 69.5 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 21 | 70.1 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 22 | 71.9 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2 | Day 23 | 74.5 percentage of participants |
p-value: 0.0004Log Rank
Secondary
Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History
Participants recorded presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe:4\]) of heartburn in participant diary. Score range was 0-4, higher score indicates greater severity. Cumulative rate of improvement calculated as percentage of participants who experienced symptom improvement. Cumulative improvement rate calculated in each subgroup of the response (improved or not improved) in participants who had medication history of any of acid suppressants. Acid suppressants include proton pump inhibitors \[PPIs\], histamine H2-receptor antagonists \[H2RAs\], or other agents \[anticholinergics or anti-gastrin drugs\]. Cumulative data collected between Day 0 and Day 23 and is reported for following time points: Days 0, 1, 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 and 23. Data not collected were shown as NA=Not Applicable.
Time frame: Up to Week 4
Population: FAS included participants who were randomized and received at least one dose of the study drug. Number analyzed is the number of participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 10 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 17 | 32.6 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 11 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 2 | 15.7 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 12 | 26.5 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 4 | 18.1 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 13 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 5 | 20.5 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 14 | 28.9 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 6 | 21.7 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 15 | 30.1 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 7 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 16 | 31.3 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 0 | 0.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 18 | 33.8 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 8 | 22.9 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 19 | 35.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 20 | 36.3 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 9 | 25.3 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 21 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 1 | 13.3 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 22 | 41.6 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 23 | 48.9 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 12 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 4 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 6 | 27.3 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 17 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 22 | 54.5 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 23 | 61.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 0 | 0.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 1 | 25.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 5 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 7 | 28.5 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 8 | 29.6 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 9 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 10 | 30.8 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 11 | 35.4 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 2 | 26.2 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 13 | 41.2 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 14 | 42.3 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 15 | 43.5 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 16 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 18 | 46.9 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 19 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 20 | 49.4 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 21 | 50.8 percentage of participants |
p-value: 0.0811Log Rank
Secondary
Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2
Participants recorded presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe:4\]) of heartburn in daily participant diary. The score range was 0-4, with the higher scores reflecting the greater severity. Cumulative rate of improvement is calculated as percentage of participants who experienced symptom improvement. The response was evaluated per Criteria 1, i.e. Improved: the participants experienced heartburn on less than 2 days of the 7 days prior to Week 2 \[Day 8 through Day 14\]; Not improved: the participants experienced heartburn on 2 days or more of the 7 days prior to Week 2 \[Day 8 through Day 14\]. Cumulative data was collected between Day 0 and Day 24 and is reported for following time points: Days 0, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24. Data not collected were shown as NA = Not Applicable.
Time frame: Day 0 to Day 24
Population: FAS included participants who were randomized and received at least one dose of the study drug. Number analyzed is the number of participants who were evaluable at each category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 9 | 3.7 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 17 | 21.6 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 13 | 11.7 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 18 | 24.7 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 11 | 6.8 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 19 | 26.6 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 14 | 14.2 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 20 | 29.2 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 10 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 21 | 31.5 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 15 | 15.4 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 22 | 34.9 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 12 | 9.3 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 23 | 39.2 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 16 | 19.1 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 24 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 0 | 0.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 24 | 55.1 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 0 | 0.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 9 | 2.2 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 10 | 4.4 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 11 | 8.1 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 12 | 12.6 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 13 | 18.5 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 14 | 22.2 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 15 | 25.2 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 16 | 26.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 17 | 28.9 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 18 | 33.3 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 19 | 35.6 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 20 | 38.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 21 | 39.5 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 22 | 41.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2 | Day 23 | 47.0 percentage of participants |
p-value: 0.1059Log Rank
Secondary
Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2
Participants recorded presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe:4\]) of heartburn in daily participant diary. The score range was 0-4, with higher scores reflecting the greater severity. Cumulative rate of improvement calculated as percentage of participants who experienced symptom improvement. The response evaluated per Criteria 2, i.e. Improved: proportion of days participant experienced heartburn during treatment period up to Week 2 \[Day 14\] was lower than that during run-in period; Not improved: proportion of days participants experienced heartburn during treatment period up to Week 2 \[Day 14\] was equal to or larger than that during run-in period. Cumulative data was collected between Day 0 and Day 24 and is reported for following time points: Days 0, 5, 9, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24. Data not collected shown as NA=Not Applicable.
Time frame: Day 0 to Day 24
Population: FAS included participants who were randomized and received at least one dose of the study drug. Number analyzed is the number of participants who were evaluable at each category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 19 | 22.1 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 0 | 0.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 5 | 2.6 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 9 | 5.2 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 11 | 6.5 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 12 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 13 | 7.8 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 14 | 13.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 15 | 14.3 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 16 | 16.9 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 17 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 18 | 19.5 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 20 | 24.9 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 21 | 27.9 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 22 | 31.3 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 23 | 41.1 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 24 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 24 | 50.9 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 16 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 0 | 0.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 21 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 5 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 17 | 19.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 9 | 1.6 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 23 | 42.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 11 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 18 | 24.6 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 12 | 4.9 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 19 | 26.2 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 13 | 8.2 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 22 | 37.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 14 | 14.8 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 20 | 29.7 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2 | Day 15 | 18.0 percentage of participants |
p-value: 0.5393Log Rank
Secondary
Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved) to Acid Suppressants in Participants Who Had a Medication History
Participants recorded presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe:4\]) of heartburn in participant diary. Score range was 0-4, higher score indicates greater severity. Cumulative rate of improvement calculated as percentage of participants who experienced symptom improvement. Cumulative improvement rate calculated in each subgroup of the response (improved or not improved) in participants who had medication history of any of acid suppressants. Acid suppressants include proton pump inhibitors \[PPIs\], histamine H2-receptor antagonists \[H2RAs\], or other agents \[anticholinergics or anti-gastrin drugs\]. Cumulative data was collected between Day 0 and Day 23 and is reported for following time points: Days 0, 1, 5, 9, 16, 19, and 20. Data not collected were shown as NA=Not Applicable.
Time frame: Up to Week 4
Population: FAS included participants who were randomized and received at least one dose of the study drug. Number analyzed is the number of participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 9 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 16 | 37.5 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 0 | 0.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 19 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 5 | NA percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 20 | 50.0 percentage of participants |
| Placebo | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 1 | 25.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 20 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 0 | 0.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 1 | 40.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 5 | 60.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 16 | NA percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 19 | 100.0 percentage of participants |
| TAK-438 10 mg | Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved) to Acid Suppressants in Participants Who Had a Medication History | Day 9 | 80.0 percentage of participants |
p-value: 0.0288Log Rank
Secondary
Percentage of Days Without Symptoms of Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N or M) at Baseline
Heartburn symptoms were collected by participant diaries. Participants recorded the presence and severity (Without symptom \[No symptom: 0, No hindrance to daily activities: 1\], With symptom \[Mild: 2, Moderate: 3, Severe: 4\]) of heartburn in a daily participant diary. The score range was 0-4, higher scores indicates greater severity. The percentage was calculated in each subgroup of the endoscopic findings where Grade N: normal mucosa; Grade M: minimal changes to the mucosa, such as erythema and/or whitish turbidity; Grade A: non-confluent mucosal breaks \<5mm in length; Grade B: non-confluent mucosal breaks ≥5mm in length; Grade C: confluent mucosal breaks \<75% circumferential; Grade D: confluent mucosal breaks \>75% circumferential.
Time frame: Up to Week 4
Population: FAS included participants who were randomized and received at least one dose of the study drug. Number analyzed is the number of participants who had endoscopic findings.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Percentage of Days Without Symptoms of Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N or M) at Baseline | Grade N | 64.15 percentage of days |
| Placebo | Percentage of Days Without Symptoms of Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N or M) at Baseline | Grade M | 60.70 percentage of days |
| TAK-438 10 mg | Percentage of Days Without Symptoms of Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N or M) at Baseline | Grade N | 76.70 percentage of days |
| TAK-438 10 mg | Percentage of Days Without Symptoms of Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N or M) at Baseline | Grade M | 67.90 percentage of days |
Comparison: Statistical analysis for Grade N of endoscopic findingsp-value: 0.14995% CI: [-1.9, 15.3]Wilcoxon Rank-Sum Test
Comparison: Statistical analysis for Grade M of endoscopic findingsp-value: 0.214695% CI: [-1.4, 10.7]Wilcoxon Rank-Sum Test
Secondary
Percentage of Days Without Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) at Week 2
Participants recorded the presence and severity of heartburn in a daily participant diary. Percentage of days without heartburn was calculated in each subgroup of the response (improved or not improved) according to Criteria 1, i.e. Improved: the participants experienced heartburn on less than 2 days of the 7 days prior to Week 2 \[Day 8 through Day 14\]; Not improved: the participants experienced heartburn on 2 days or more of the 7 days prior to Week 2 \[Day 8 through Day 14\] and Criteria 2, i.e. Improved: the proportion of days the participants experienced heartburn during the treatment period up to Week 2 \[Day 14\] was lower than that during the run-in period; Not improved: the proportion of days the participants experienced heartburn during the treatment period up to Week 2 \[Day 14\] was equal to or larger than that during the run-in period.
Time frame: Up to Week 4
Population: FAS included participants who were randomized and received at least one dose of the study drug. Number analyzed is the number of participants who were evaluable at each category.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Percentage of Days Without Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) at Week 2 | Criteria 1, Improved | 92.00 percentage of days |
| Placebo | Percentage of Days Without Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) at Week 2 | Criteria 1, Not Improved | 50.95 percentage of days |
| Placebo | Percentage of Days Without Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) at Week 2 | Criteria 2, Improved | 71.40 percentage of days |
| Placebo | Percentage of Days Without Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) at Week 2 | Criteria 2, Not Improved | 39.30 percentage of days |
| TAK-438 10 mg | Percentage of Days Without Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) at Week 2 | Criteria 2, Not Improved | 24.15 percentage of days |
| TAK-438 10 mg | Percentage of Days Without Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) at Week 2 | Criteria 1, Improved | 96.00 percentage of days |
| TAK-438 10 mg | Percentage of Days Without Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) at Week 2 | Criteria 2, Improved | 81.15 percentage of days |
| TAK-438 10 mg | Percentage of Days Without Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) at Week 2 | Criteria 1, Not Improved | 48.05 percentage of days |
Comparison: Statistical analysis for criteria 1, improved responsep-value: 0.047895% CI: [0, 5.3]Wilcoxon Rank-Sum Test
Comparison: Statistical analysis for criteria 1, not improved responsep-value: 0.896395% CI: [-6.1, 6]Wilcoxon Rank-Sum Test
Comparison: Statistical analysis for criteria 2, improved responsep-value: 0.01295% CI: [0, 10.7]Wilcoxon Rank-Sum Test
Comparison: Statistical analysis for criteria 2, not improved responsep-value: 0.087195% CI: [-17.4, 0]Wilcoxon Rank-Sum Test
Secondary
Percentage of Days Without Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) to Acid Suppressants in Participants Who Had a Medication History
Heartburn symptoms were collected by participant diaries. Participants recorded the presence and severity (Without symptom \[No symptom: 0, No hindrance to daily activities: 1\], With symptom \[Mild: 2, Moderate: 3, Severe: 4\]) of heartburn in a daily participant diary. The score range was 0-4, higher score indicates greater severity. The percentage was calculated in each subgroup of the response (improved or not improved) in the participants who had a medication history of any of acid suppressants. The acid suppressants include proton pump inhibitors \[PPIs\], histamine H2-receptor antagonists \[H2RAs\], or other agents \[anticholinergics or anti-gastrin drugs\].
Time frame: Up to Week 4
Population: FAS included participants who were randomized and received at least one dose of the study drug. Number analyzed is the number of participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Percentage of Days Without Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) to Acid Suppressants in Participants Who Had a Medication History | Improved | 61.30 percentage of days |
| Placebo | Percentage of Days Without Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) to Acid Suppressants in Participants Who Had a Medication History | Not Improved | 49.30 percentage of days |
| TAK-438 10 mg | Percentage of Days Without Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) to Acid Suppressants in Participants Who Had a Medication History | Improved | 71.40 percentage of days |
| TAK-438 10 mg | Percentage of Days Without Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) to Acid Suppressants in Participants Who Had a Medication History | Not Improved | 80.80 percentage of days |
Comparison: Statistical analysis for improved responsep-value: 0.188595% CI: [-2.7, 14.3]Wilcoxon Rank-Sum Test
Comparison: Statistical analysis for not improved responsep-value: 0.233795% CI: [-19.2, 75]Wilcoxon Rank-Sum Test
Secondary
Percentage of Days Without Symptoms of Heartburn Stratified by Subgroup of Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M)
Heartburn symptoms were collected by participant diaries. Participants recorded the presence and severity (Without symptom \[No symptom: 0, No hindrance to daily activities: 1\], With symptom \[Mild: 2, Moderate: 3, Severe: 4\]) of heartburn in a daily participant diary. The score range was 0-4, higher scores indicates greater severity. The percentage was calculated in each subgroup (response; Grade N and improved, response; Grade N and not improved, response; Grade M and improved, response; Grade M and not improved) according to Criteria 1 and 2. The modified LA classification Grade N indicates the participants with normal mucosa and Grade M indicates the participants with minimal changes to the mucosa.
Time frame: Up to Week 4
Population: FAS included participants who were randomized and received at least one dose of the study drug. Number analyzed is the number of participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Percentage of Days Without Symptoms of Heartburn Stratified by Subgroup of Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Criteria 1, Grade N and Improved | 93.00 percentage of days |
| Placebo | Percentage of Days Without Symptoms of Heartburn Stratified by Subgroup of Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Criteria 1, Grade N and Not Improved | 53.60 percentage of days |
| Placebo | Percentage of Days Without Symptoms of Heartburn Stratified by Subgroup of Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Criteria 1, Grade M and Improved | 89.30 percentage of days |
| Placebo | Percentage of Days Without Symptoms of Heartburn Stratified by Subgroup of Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Criteria 1, Grade M and Not Improved | 49.05 percentage of days |
| Placebo | Percentage of Days Without Symptoms of Heartburn Stratified by Subgroup of Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Criteria 2, Grade N and Improved | 69.00 percentage of days |
| Placebo | Percentage of Days Without Symptoms of Heartburn Stratified by Subgroup of Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Criteria 2, Grade N and Not Improved | 50.00 percentage of days |
| Placebo | Percentage of Days Without Symptoms of Heartburn Stratified by Subgroup of Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Criteria 2, Grade M and Improved | 73.30 percentage of days |
| Placebo | Percentage of Days Without Symptoms of Heartburn Stratified by Subgroup of Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Criteria 2, Grade M and Not Improved | 33.90 percentage of days |
| TAK-438 10 mg | Percentage of Days Without Symptoms of Heartburn Stratified by Subgroup of Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Criteria 2, Grade M and Not Improved | 25.00 percentage of days |
| TAK-438 10 mg | Percentage of Days Without Symptoms of Heartburn Stratified by Subgroup of Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Criteria 1, Grade N and Improved | 92.90 percentage of days |
| TAK-438 10 mg | Percentage of Days Without Symptoms of Heartburn Stratified by Subgroup of Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Criteria 2, Grade N and Improved | 79.30 percentage of days |
| TAK-438 10 mg | Percentage of Days Without Symptoms of Heartburn Stratified by Subgroup of Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Criteria 1, Grade N and Not Improved | 53.60 percentage of days |
| TAK-438 10 mg | Percentage of Days Without Symptoms of Heartburn Stratified by Subgroup of Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Criteria 2, Grade M and Improved | 82.10 percentage of days |
| TAK-438 10 mg | Percentage of Days Without Symptoms of Heartburn Stratified by Subgroup of Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Criteria 1, Grade M and Improved | 96.40 percentage of days |
| TAK-438 10 mg | Percentage of Days Without Symptoms of Heartburn Stratified by Subgroup of Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Criteria 2, Grade N and Not Improved | 22.95 percentage of days |
| TAK-438 10 mg | Percentage of Days Without Symptoms of Heartburn Stratified by Subgroup of Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Criteria 1, Grade M and Not Improved | 44.40 percentage of days |
Comparison: Statistical analysis for Criteria 1, Grade N and improved responsep-value: 0.663195% CI: [-5, 3.5]Wilcoxon Rank-Sum Test
Comparison: Statistical analysis for Criteria 1, Grade N and not improved responsep-value: 0.562795% CI: [-7.1, 13.9]Wilcoxon Rank-Sum Test
Comparison: Statistical analysis for Criteria 1, Grade M and improved responsep-value: 0.004295% CI: [0, 8]Wilcoxon Rank-Sum Test
Comparison: Statistical analysis for Criteria 1, Grade M and not improved responsep-value: 0.645295% CI: [-9.4, 6.4]Wilcoxon Rank-Sum Test
Comparison: Statistical analysis for Criteria 2, Grade N and improved responsep-value: 0.037695% CI: [0, 17.8]Wilcoxon Rank-Sum Test
Comparison: Statistical analysis for Criteria 2, Grade N and not improved responsep-value: 0.1695% CI: [-35.7, 3.6]Wilcoxon Rank-Sum Test
Comparison: Statistical analysis for Criteria 2, Grade M and improved responsep-value: 0.103295% CI: [0, 10.7]Wilcoxon Rank-Sum Test
Comparison: Statistical analysis for Criteria 2, Grade M and not improved responsep-value: 0.261395% CI: [-14.3, 0.2]Wilcoxon Rank-Sum Test
Secondary
Severity of Symptoms of Heartburn in Subgroup Stratified by Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M)
Heartburn symptoms were collected by participant diaries. Participants recorded the presence and severity (Without symptom \[No symptom: 0, No hindrance to daily activities: 1\], With symptom \[Mild: 2, Moderate: 3, Severe: 4\]) of heartburn in a daily participant diary. The score range was 0-4, with the higher scores reflecting the greater severity. The mean severity of heartburn was calculated in each subgroup (response; Grade N and improved, response; Grade N and not improved, response; Grade M and improved, response; Grade M and not improved) according to criteria 1 and 2. The modified LA classification Grade N indicates the participants with normal mucosa and Grade M indicates the participants with minimal changes to the mucosa.
Time frame: Up to Week 4
Population: FAS included participants who were randomized and received at least one dose of the study drug. Number analyzed is the number of participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Severity of Symptoms of Heartburn in Subgroup Stratified by Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Criteria 1, Grade M and Not Improved | 1.430 score on a scale |
| Placebo | Severity of Symptoms of Heartburn in Subgroup Stratified by Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Criteria 2, Grade N and Improved | 1.000 score on a scale |
| Placebo | Severity of Symptoms of Heartburn in Subgroup Stratified by Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Criteria 2, Grade N and Not Improved | 1.460 score on a scale |
| Placebo | Severity of Symptoms of Heartburn in Subgroup Stratified by Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Criteria 2, Grade M and Improved | 0.890 score on a scale |
| Placebo | Severity of Symptoms of Heartburn in Subgroup Stratified by Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Criteria 2, Grade M and Not Improved | 1.645 score on a scale |
| Placebo | Severity of Symptoms of Heartburn in Subgroup Stratified by Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Criteria 1, Grade N and Improved | 0.510 score on a scale |
| Placebo | Severity of Symptoms of Heartburn in Subgroup Stratified by Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Criteria 1, Grade N and Not Improved | 1.375 score on a scale |
| Placebo | Severity of Symptoms of Heartburn in Subgroup Stratified by Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Criteria 1, Grade M and Improved | 0.420 score on a scale |
| TAK-438 10 mg | Severity of Symptoms of Heartburn in Subgroup Stratified by Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Criteria 1, Grade M and Improved | 0.280 score on a scale |
| TAK-438 10 mg | Severity of Symptoms of Heartburn in Subgroup Stratified by Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Criteria 1, Grade M and Not Improved | 1.520 score on a scale |
| TAK-438 10 mg | Severity of Symptoms of Heartburn in Subgroup Stratified by Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Criteria 2, Grade M and Not Improved | 1.790 score on a scale |
| TAK-438 10 mg | Severity of Symptoms of Heartburn in Subgroup Stratified by Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Criteria 2, Grade N and Improved | 0.640 score on a scale |
| TAK-438 10 mg | Severity of Symptoms of Heartburn in Subgroup Stratified by Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Criteria 1, Grade N and Not Improved | 1.240 score on a scale |
| TAK-438 10 mg | Severity of Symptoms of Heartburn in Subgroup Stratified by Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Criteria 2, Grade N and Not Improved | 1.695 score on a scale |
| TAK-438 10 mg | Severity of Symptoms of Heartburn in Subgroup Stratified by Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Criteria 1, Grade N and Improved | 0.430 score on a scale |
| TAK-438 10 mg | Severity of Symptoms of Heartburn in Subgroup Stratified by Both the Response at Week 2 and the Endoscopic Findings (the Modified LA Classification Grade N or M) | Criteria 2, Grade M and Improved | 0.710 score on a scale |
Comparison: Statistical analysis for Criteria 1, Grade N and improved responsep-value: 0.784595% CI: [-0.23, 0.16]Wilcoxon Rank-Sum Test
Comparison: Statistical analysis for Criteria 1, Grade N and not improved responsep-value: 0.445695% CI: [-0.33, 0.17]Wilcoxon Rank-Sum Test
Comparison: Statistical analysis for Criteria 1, Grade M and improved responsep-value: 0.0295% CI: [-0.29, -0.02]Wilcoxon Rank-Sum Test
Comparison: Statistical analysis for Criteria 1, Grade M and not improved responsep-value: 0.467395% CI: [-0.1, 0.22]Wilcoxon Rank-Sum Test
Comparison: Statistical analysis for Criteria 2, Grade N and improved responsep-value: 0.009595% CI: [-0.53, -0.07]Wilcoxon Rank-Sum Test
Comparison: Statistical analysis for Criteria 2, Grade N and not improved responsep-value: 0.16595% CI: [-0.16, 0.71]Wilcoxon Rank-Sum Test
Comparison: Statistical analysis for Criteria 2, Grade M and improved responsep-value: 0.247595% CI: [-0.24, 0.07]Wilcoxon Rank-Sum Test
Comparison: Statistical analysis for Criteria 2, Grade M and not improvedp-value: 0.236795% CI: [-0.09, 0.32]Wilcoxon Rank-Sum Test
Secondary
Severity of Symptoms of Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N or M) at Baseline
Heartburn symptoms were collected by participant diaries. Participants recorded the presence and severity (Without symptom \[No symptom:0, No hindrance to daily activities:1\], With symptom \[Mild:2, Moderate:3, Severe:4\]) of heartburn in a daily participant diary. The score range was 0-4, with the higher scores reflecting the greater severity. The severity of heartburn was calculated in each subgroup of the endoscopic findings where Grade N: normal mucosa; Grade M: minimal changes to the mucosa, such as erythema and/or whitish turbidity; Grade A: non-confluent mucosal breaks \<5mm in length; Grade B: non-confluent mucosal breaks ≥5mm in length; Grade C: confluent mucosal breaks \<75% circumferential; Grade D: confluent mucosal breaks \>75% circumferential.
Time frame: Up to Week 4
Population: FAS included participants who were randomized and received at least one dose of the study drug. Number analyzed is the number of participants who had endoscopic findings.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Severity of Symptoms of Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N or M) at Baseline | Grade M | 1.180 score on a scale |
| Placebo | Severity of Symptoms of Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N or M) at Baseline | Grade N | 1.070 score on a scale |
| TAK-438 10 mg | Severity of Symptoms of Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N or M) at Baseline | Grade N | 0.850 score on a scale |
| TAK-438 10 mg | Severity of Symptoms of Heartburn in Subgroup Stratified by Endoscopic Findings (the Modified LA Classification Grade N or M) at Baseline | Grade M | 1.110 score on a scale |
Comparison: Statistical analysis for Grade N of endoscopic findingsp-value: 0.075795% CI: [-0.43, 0.02]Wilcoxon Rank-Sum Test
Comparison: Statistical analysis for Grade M of endoscopic findingsp-value: 0.383795% CI: [-0.22, 0.09]Wilcoxon Rank-Sum Test
Secondary
Severity of Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) at Week 2
Participants recorded the presence and severity (Without symptom \[No symptom: 0, No hindrance to daily activities: 1\], With symptom \[Mild: 2, Moderate: 3, Severe: 4\]) of heartburn in a daily participant diary. The score range was 0-4, the higher scores indicates greater severity. The severity was calculated in each subgroup of response (improved or not improved) according to Criteria 1, i.e. Improved: participants experienced heartburn on less than 2 days of the 7 days prior to Week 2 \[Day 8 through Day 14\]; Not improved: participants experienced heartburn on 2 days or more of the 7 days prior to Week 2 \[Day 8 through Day 14\] and Criteria 2, i.e. Improved: proportion of days the participants experienced heartburn during the treatment period up to Week 2 \[Day 14\] was lower than that during the run-in period; Not improved: proportion of days the participants experienced heartburn during the treatment period up to Week 2 \[Day 14\] was equal to or larger than that during the run-in period.
Time frame: Up to Week 4
Population: FAS included participants who were randomized and received at least one dose of the study drug. Number analyzed is the number of participants who were evaluable at each category.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Severity of Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) at Week 2 | Criteria 1, Improved | 0.420 score on a scale |
| Placebo | Severity of Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) at Week 2 | Criteria 1, Not Improved | 1.430 score on a scale |
| Placebo | Severity of Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) at Week 2 | Criteria 2, Improved | 0.960 score on a scale |
| Placebo | Severity of Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) at Week 2 | Criteria 2, Not Improved | 1.610 score on a scale |
| TAK-438 10 mg | Severity of Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) at Week 2 | Criteria 2, Not Improved | 1.740 score on a scale |
| TAK-438 10 mg | Severity of Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) at Week 2 | Criteria 1, Improved | 0.310 score on a scale |
| TAK-438 10 mg | Severity of Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) at Week 2 | Criteria 2, Improved | 0.675 score on a scale |
| TAK-438 10 mg | Severity of Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) at Week 2 | Criteria 1, Not Improved | 1.420 score on a scale |
Comparison: Statistical analysis for criteria 1, improved responsep-value: 0.050595% CI: [-0.21, 0]Wilcoxon Rank-Sum Test
Comparison: Statistical analysis for criteria 1, not improved responsep-value: 0.813895% CI: [-0.12, 0.15]Wilcoxon Rank-Sum Test
Comparison: Statistical analysis for criteria 2, improved responsep-value: 0.012995% CI: [-0.28, -0.03]Wilcoxon Rank-Sum Test
Comparison: Statistical analysis for criteria 2, not improved responsep-value: 0.076595% CI: [-0.01, 0.36]Wilcoxon Rank-Sum Test
Secondary
Severity of Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) to Acid Suppressants in Participants Who Had a Medication History
Heartburn symptoms were collected by participant diaries. Participants recorded the presence and severity (Without symptom \[No symptom: 0, No hindrance to daily activities: 1\], With symptom \[Mild: 2, Moderate: 3, Severe: 4\]) of heartburn in a daily participant diary. The score range was 0-4, with the higher scores reflecting the greater severity. The mean severity of heartburn was calculated in each subgroup of the response (improved or not improved) in the participants who had a medication history of any of acid suppressants. The acid suppressants include proton pump inhibitors \[PPIs\], histamine H2-receptor antagonists \[H2RAs\], or other agents \[anticholinergics or anti-gastrin drugs\].
Time frame: Up to Week 4
Population: FAS included participants who were randomized and received at least one dose of the study drug. Number analyzed is the number of participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Severity of Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) to Acid Suppressants in Participants Who Had a Medication History | Improved | 1.150 score on a scale |
| Placebo | Severity of Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) to Acid Suppressants in Participants Who Had a Medication History | Not Improved | 1.280 score on a scale |
| TAK-438 10 mg | Severity of Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) to Acid Suppressants in Participants Who Had a Medication History | Improved | 1.040 score on a scale |
| TAK-438 10 mg | Severity of Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) to Acid Suppressants in Participants Who Had a Medication History | Not Improved | 1.030 score on a scale |
Comparison: Statistical analysis for improved responsep-value: 0.148895% CI: [-0.42, 0.04]Wilcoxon Rank-Sum Test
Comparison: Statistical analysis for not improved responsep-value: 0.377895% CI: [-1.57, 0.69]Wilcoxon Rank-Sum Test