Trial Outcomes & Findings for Phase 3 Study of TAK-438 10 mg in the Treatment of Non-Erosive Gastroesophageal Reflux Disease (NERD) (NCT NCT02954848)
NCT ID: NCT02954848
Last Updated: 2019-08-02
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
484 participants
Primary outcome timeframe
Up to Week 4
Results posted on
2019-08-02
Participant Flow
Participants took part in the study at 44 investigative sites in Japan from 15 November 2016 to 26 February 2018.
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.
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
245
|
239
|
|
Overall Study
Treated
|
245
|
238
|
|
Overall Study
COMPLETED
|
243
|
234
|
|
Overall Study
NOT COMPLETED
|
2
|
5
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
Randomized but Not Treated
|
0
|
1
|
|
Overall Study
Adverse Event
|
2
|
3
|
|
Overall Study
Withdrawal by Participant
|
0
|
1
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Placebo
n=245 Participants
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.
|
TAK-438 10 mg
n=239 Participants
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.
|
Total
n=484 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
51.8 years
STANDARD_DEVIATION 15.38 • n=245 Participants
|
52.8 years
STANDARD_DEVIATION 14.37 • n=239 Participants
|
52.3 years
STANDARD_DEVIATION 14.88 • n=484 Participants
|
|
Sex: Female, Male
Female
|
140 Participants
n=245 Participants
|
161 Participants
n=239 Participants
|
301 Participants
n=484 Participants
|
|
Sex: Female, Male
Male
|
105 Participants
n=245 Participants
|
78 Participants
n=239 Participants
|
183 Participants
n=484 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
Japan
|
245 Participants
n=245 Participants
|
239 Participants
n=239 Participants
|
484 Participants
n=484 Participants
|
|
Height
|
161.7 cm
STANDARD_DEVIATION 8.62 • n=245 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
160.5 cm
STANDARD_DEVIATION 9.29 • n=237 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
161.1 cm
STANDARD_DEVIATION 8.97 • n=482 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
|
Weight
|
59.6 kg
STANDARD_DEVIATION 12.04 • n=245 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
58.7 kg
STANDARD_DEVIATION 11.15 • n=237 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
59.2 kg
STANDARD_DEVIATION 11.61 • n=482 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
|
Body Mass Index (BMI)
|
22.67 kg/m^2
STANDARD_DEVIATION 3.431 • n=245 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
22.71 kg/m^2
STANDARD_DEVIATION 3.375 • n=237 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
22.69 kg/m^2
STANDARD_DEVIATION 3.400 • n=482 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
|
Smoking Classification
Never Smoked
|
124 Participants
n=245 Participants
|
128 Participants
n=239 Participants
|
252 Participants
n=484 Participants
|
|
Smoking Classification
Current Smoker
|
52 Participants
n=245 Participants
|
44 Participants
n=239 Participants
|
96 Participants
n=484 Participants
|
|
Smoking Classification
Ex-smoker
|
69 Participants
n=245 Participants
|
67 Participants
n=239 Participants
|
136 Participants
n=484 Participants
|
|
Consumption of Alcohol
Drank Every Day
|
59 Participants
n=245 Participants
|
46 Participants
n=239 Participants
|
105 Participants
n=484 Participants
|
|
Consumption of Alcohol
Drank a Couple of Days Per Week
|
62 Participants
n=245 Participants
|
63 Participants
n=239 Participants
|
125 Participants
n=484 Participants
|
|
Consumption of Alcohol
Drank a Couple of Days Per Month
|
54 Participants
n=245 Participants
|
54 Participants
n=239 Participants
|
108 Participants
n=484 Participants
|
|
Consumption of Alcohol
Never Drank
|
70 Participants
n=245 Participants
|
76 Participants
n=239 Participants
|
146 Participants
n=484 Participants
|
|
Consumption of Caffeine
Had Caffeine Consumption
|
192 Participants
n=245 Participants
|
190 Participants
n=239 Participants
|
382 Participants
n=484 Participants
|
|
Consumption of Caffeine
Had No Caffeine Consumption
|
53 Participants
n=245 Participants
|
49 Participants
n=239 Participants
|
102 Participants
n=484 Participants
|
|
Endoscopic Findings by Principal Investigator (PI)
Grade N
|
82 Participants
n=245 Participants
|
81 Participants
n=239 Participants
|
163 Participants
n=484 Participants
|
|
Endoscopic Findings by Principal Investigator (PI)
Grade M
|
163 Participants
n=245 Participants
|
158 Participants
n=239 Participants
|
321 Participants
n=484 Participants
|
|
Endoscopic Findings by Central Adjudication Committee (CAC)
Grade M
|
168 Participants
n=245 Participants
|
157 Participants
n=239 Participants
|
325 Participants
n=484 Participants
|
|
Endoscopic Findings by Central Adjudication Committee (CAC)
Grade N
|
77 Participants
n=245 Participants
|
82 Participants
n=239 Participants
|
159 Participants
n=484 Participants
|
|
Barrett's Mucosa
Yes (Less than 3 cm)
|
56 Participants
n=245 Participants
|
51 Participants
n=239 Participants
|
107 Participants
n=484 Participants
|
|
Barrett's Mucosa
No
|
189 Participants
n=245 Participants
|
188 Participants
n=239 Participants
|
377 Participants
n=484 Participants
|
|
Esophageal Hiatal Hernia
Yes (2 cm or More)
|
17 Participants
n=245 Participants
|
18 Participants
n=239 Participants
|
35 Participants
n=484 Participants
|
|
Esophageal Hiatal Hernia
Yes (Less than 2 cm)
|
82 Participants
n=245 Participants
|
85 Participants
n=239 Participants
|
167 Participants
n=484 Participants
|
|
Esophageal Hiatal Hernia
No
|
146 Participants
n=245 Participants
|
136 Participants
n=239 Participants
|
282 Participants
n=484 Participants
|
|
Severity of Symptoms, Heartburn
|
1.641 score on a scale
STANDARD_DEVIATION 0.5747 • n=245 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
1.765 score on a scale
STANDARD_DEVIATION 0.6171 • n=238 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
1.702 score on a scale
STANDARD_DEVIATION 0.5986 • n=483 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
|
Severity of Symptoms, Regurgitation
|
1.074 score on a scale
STANDARD_DEVIATION 0.8398 • n=245 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
1.109 score on a scale
STANDARD_DEVIATION 0.9092 • n=238 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
1.091 score on a scale
STANDARD_DEVIATION 0.8739 • n=483 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
|
Use of Proton Pump Inhibitors (PPIs) Within 180 Days Prior to Informed Consent (IC)
Yes
|
45 Participants
n=245 Participants
|
55 Participants
n=239 Participants
|
100 Participants
n=484 Participants
|
|
Use of Proton Pump Inhibitors (PPIs) Within 180 Days Prior to Informed Consent (IC)
No
|
200 Participants
n=245 Participants
|
184 Participants
n=239 Participants
|
384 Participants
n=484 Participants
|
|
Use of H2-Receptor Antagonists (H2RA) Within 180 Days Prior to IC
Yes
|
29 Participants
n=245 Participants
|
28 Participants
n=239 Participants
|
57 Participants
n=484 Participants
|
|
Use of H2-Receptor Antagonists (H2RA) Within 180 Days Prior to IC
No
|
216 Participants
n=245 Participants
|
211 Participants
n=239 Participants
|
427 Participants
n=484 Participants
|
|
Use of Other Agents (Anticholinergics or Anti-gastrin Drugs) within 180 Days Prior to IC
Yes
|
24 Participants
n=245 Participants
|
22 Participants
n=239 Participants
|
46 Participants
n=484 Participants
|
|
Use of Other Agents (Anticholinergics or Anti-gastrin Drugs) within 180 Days Prior to IC
No
|
221 Participants
n=245 Participants
|
217 Participants
n=239 Participants
|
438 Participants
n=484 Participants
|
|
Response to Acid Suppressants
Heartburn has been Resolved
|
31 Participants
n=91 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
45 Participants
n=93 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
76 Participants
n=184 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
|
Response to Acid Suppressants
Heartburn has not been Resolved but Relieved
|
52 Participants
n=91 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
43 Participants
n=93 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
95 Participants
n=184 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
|
Response to Acid Suppressants
Heartburn has Remained Unchanged
|
8 Participants
n=91 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
5 Participants
n=93 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
13 Participants
n=184 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
|
Response to Acid Suppressants
Improved
|
83 Participants
n=91 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
88 Participants
n=93 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
171 Participants
n=184 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
|
Response to Acid Suppressants
Not Improved
|
8 Participants
n=91 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
5 Participants
n=93 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
13 Participants
n=184 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
|
History of H. pylori Eradication
Within the Last Year
|
2 Participants
n=245 Participants
|
1 Participants
n=239 Participants
|
3 Participants
n=484 Participants
|
|
History of H. pylori Eradication
More than One Year Before
|
58 Participants
n=245 Participants
|
49 Participants
n=239 Participants
|
107 Participants
n=484 Participants
|
|
History of H. pylori Eradication
No
|
185 Participants
n=245 Participants
|
189 Participants
n=239 Participants
|
374 Participants
n=484 Participants
|
|
Serological Determination for H. pylori
Positive
|
37 Participants
n=245 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
28 Participants
n=237 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
65 Participants
n=482 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
|
Serological Determination for H. pylori
Negative
|
208 Participants
n=245 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
209 Participants
n=237 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
417 Participants
n=482 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
|
Gastrin
|
91.6 pg/mL
STANDARD_DEVIATION 53.29 • n=243 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
103.1 pg/mL
STANDARD_DEVIATION 182.68 • n=237 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
97.3 pg/mL
STANDARD_DEVIATION 133.83 • n=480 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
|
Ratio of Pepsinogen I to Pepsinogen II
|
7.63 ratio
STANDARD_DEVIATION 2.722 • n=243 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
7.57 ratio
STANDARD_DEVIATION 2.442 • n=237 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
7.60 ratio
STANDARD_DEVIATION 2.585 • n=480 Participants • Number analyzed are the participants who were evaluated for this baseline measure.
|
|
Factors and Improvement: Physical Factors, Kyphosis
Yes
|
4 Participants
n=245 Participants
|
8 Participants
n=239 Participants
|
12 Participants
n=484 Participants
|
|
Factors and Improvement: Physical Factors, Kyphosis
No
|
241 Participants
n=245 Participants
|
231 Participants
n=239 Participants
|
472 Participants
n=484 Participants
|
|
Factors and Improvement: Physical Factors, Evident Obesity
Yes
|
14 Participants
n=245 Participants
|
15 Participants
n=239 Participants
|
29 Participants
n=484 Participants
|
|
Factors and Improvement: Physical Factors, Evident Obesity
No
|
231 Participants
n=245 Participants
|
224 Participants
n=239 Participants
|
455 Participants
n=484 Participants
|
|
Factors and Improvement: Movement, Forward Flexion
Yes
|
105 Participants
n=245 Participants
|
83 Participants
n=239 Participants
|
188 Participants
n=484 Participants
|
|
Factors and Improvement: Movement, Forward Flexion
No
|
140 Participants
n=245 Participants
|
156 Participants
n=239 Participants
|
296 Participants
n=484 Participants
|
|
Factors and Improvement: Movement, Lying in Bed
Yes
|
99 Participants
n=245 Participants
|
89 Participants
n=239 Participants
|
188 Participants
n=484 Participants
|
|
Factors and Improvement: Movement, Lying in Bed
No
|
146 Participants
n=245 Participants
|
150 Participants
n=239 Participants
|
296 Participants
n=484 Participants
|
|
Factors and Improvement: Movement, Other
Yes
|
13 Participants
n=245 Participants
|
12 Participants
n=239 Participants
|
25 Participants
n=484 Participants
|
|
Factors and Improvement: Movement, Other
No
|
232 Participants
n=245 Participants
|
227 Participants
n=239 Participants
|
459 Participants
n=484 Participants
|
|
Factors and Improvement: Diet, Fatty Foods (Fried Foods, Stodge, etc.)
Yes
|
165 Participants
n=245 Participants
|
156 Participants
n=239 Participants
|
321 Participants
n=484 Participants
|
|
Factors and Improvement: Diet, Fatty Foods (Fried Foods, Stodge, etc.)
No
|
80 Participants
n=245 Participants
|
83 Participants
n=239 Participants
|
163 Participants
n=484 Participants
|
|
Factors and Improvement: Diet, Carbohydrates (Grains, Potatoes, etc.)
Yes
|
115 Participants
n=245 Participants
|
90 Participants
n=239 Participants
|
205 Participants
n=484 Participants
|
|
Factors and Improvement: Diet, Carbohydrates (Grains, Potatoes, etc.)
No
|
130 Participants
n=245 Participants
|
149 Participants
n=239 Participants
|
279 Participants
n=484 Participants
|
|
Factors and Improvement: Diet, Sweet Foods (Chocolate, etc.)
Yes
|
87 Participants
n=245 Participants
|
78 Participants
n=239 Participants
|
165 Participants
n=484 Participants
|
|
Factors and Improvement: Diet, Sweet Foods (Chocolate, etc.)
No
|
158 Participants
n=245 Participants
|
161 Participants
n=239 Participants
|
319 Participants
n=484 Participants
|
|
Factors and Improvement: Diet, Acidic Foods (Citrus Fruits, Carb. Beverage)
Yes
|
79 Participants
n=245 Participants
|
66 Participants
n=239 Participants
|
145 Participants
n=484 Participants
|
|
Factors and Improvement: Diet, Acidic Foods (Citrus Fruits, Carb. Beverage)
No
|
166 Participants
n=245 Participants
|
173 Participants
n=239 Participants
|
339 Participants
n=484 Participants
|
|
Factors and Improvement: Diet, Spices (Pepper, Curry, etc.)
Yes
|
83 Participants
n=245 Participants
|
77 Participants
n=239 Participants
|
160 Participants
n=484 Participants
|
|
Factors and Improvement: Diet, Spices (Pepper, Curry, etc.)
No
|
162 Participants
n=245 Participants
|
162 Participants
n=239 Participants
|
324 Participants
n=484 Participants
|
|
Factors and Improvement: Diet, Other
Yes
|
5 Participants
n=245 Participants
|
13 Participants
n=239 Participants
|
18 Participants
n=484 Participants
|
|
Factors and Improvement: Diet, Other
No
|
240 Participants
n=245 Participants
|
226 Participants
n=239 Participants
|
466 Participants
n=484 Participants
|
|
Factors and Improvement: Habits, Smoking
Yes
|
29 Participants
n=245 Participants
|
19 Participants
n=239 Participants
|
48 Participants
n=484 Participants
|
|
Factors and Improvement: Habits, Smoking
No
|
216 Participants
n=245 Participants
|
220 Participants
n=239 Participants
|
436 Participants
n=484 Participants
|
|
Factors and Improvement: Habits, Caffeine Ingestion
Yes
|
112 Participants
n=245 Participants
|
112 Participants
n=239 Participants
|
224 Participants
n=484 Participants
|
|
Factors and Improvement: Habits, Caffeine Ingestion
No
|
133 Participants
n=245 Participants
|
127 Participants
n=239 Participants
|
260 Participants
n=484 Participants
|
|
Factors and Improvement: Habits, Drinking Alcohol
Yes
|
79 Participants
n=245 Participants
|
68 Participants
n=239 Participants
|
147 Participants
n=484 Participants
|
|
Factors and Improvement: Habits, Drinking Alcohol
No
|
166 Participants
n=245 Participants
|
171 Participants
n=239 Participants
|
337 Participants
n=484 Participants
|
|
Factors and Improvement: Above Factors are NA or cannot be Specified
Yes
|
4 Participants
n=245 Participants
|
8 Participants
n=239 Participants
|
12 Participants
n=484 Participants
|
|
Factors and Improvement: Above Factors are NA or cannot be Specified
No
|
241 Participants
n=245 Participants
|
231 Participants
n=239 Participants
|
472 Participants
n=484 Participants
|
|
Factors and Improvement: Improving Lifestyle
Yes
|
84 Participants
n=245 Participants
|
97 Participants
n=239 Participants
|
181 Participants
n=484 Participants
|
|
Factors and Improvement: Improving Lifestyle
No
|
161 Participants
n=245 Participants
|
142 Participants
n=239 Participants
|
303 Participants
n=484 Participants
|
PRIMARY outcome
Timeframe: Up to Week 4Population: Full analysis set (FAS) included participants who were randomized and received at least one dose of the study drug.
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.
Outcome measures
| Measure |
Placebo
n=245 Participants
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.
|
TAK-438 10 mg
n=238 Participants
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.
|
|---|---|---|
|
Percentage of Days Without Symptoms of Heartburn
|
61.50 percentage of days
Interval 0.0 to 100.0
|
72.55 percentage of days
Interval 0.0 to 100.0
|
PRIMARY outcome
Timeframe: Day 0 to Day 24Population: FAS included participants who were randomized and received at least one dose of the study drug.
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.
Outcome measures
| Measure |
Placebo
n=245 Participants
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.
|
TAK-438 10 mg
n=238 Participants
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.
|
|---|---|---|
|
Cumulative Rate of Improvement in Symptoms of Heartburn
Day 0
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Cumulative Rate of Improvement in Symptoms of Heartburn
Day 1
|
14.7 percentage of participants
|
23.1 percentage of participants
|
|
Cumulative Rate of Improvement in Symptoms of Heartburn
Day 2
|
15.9 percentage of participants
|
24.4 percentage of participants
|
|
Cumulative Rate of Improvement in Symptoms of Heartburn
Day 3
|
16.3 percentage of participants
|
25.2 percentage of participants
|
|
Cumulative Rate of Improvement in Symptoms of Heartburn
Day 4
|
17.6 percentage of participants
|
26.1 percentage of participants
|
|
Cumulative Rate of Improvement in Symptoms of Heartburn
Day 5
|
18.8 percentage of participants
|
28.2 percentage of participants
|
|
Cumulative Rate of Improvement in Symptoms of Heartburn
Day 6
|
19.2 percentage of participants
|
30.4 percentage of participants
|
|
Cumulative Rate of Improvement in Symptoms of Heartburn
Day 7
|
20.0 percentage of participants
|
32.5 percentage of participants
|
|
Cumulative Rate of Improvement in Symptoms of Heartburn
Day 8
|
21.2 percentage of participants
|
32.9 percentage of participants
|
|
Cumulative Rate of Improvement in Symptoms of Heartburn
Day 9
|
23.7 percentage of participants
|
34.2 percentage of participants
|
|
Cumulative Rate of Improvement in Symptoms of Heartburn
Day 10
|
NA percentage of participants
Data was not collected at this time point.
|
35.5 percentage of participants
|
|
Cumulative Rate of Improvement in Symptoms of Heartburn
Day 11
|
25.7 percentage of participants
|
38.5 percentage of participants
|
|
Cumulative Rate of Improvement in Symptoms of Heartburn
Day 12
|
27.3 percentage of participants
|
41.1 percentage of participants
|
|
Cumulative Rate of Improvement in Symptoms of Heartburn
Day 13
|
29.0 percentage of participants
|
44.6 percentage of participants
|
|
Cumulative Rate of Improvement in Symptoms of Heartburn
Day 14
|
30.6 percentage of participants
|
46.7 percentage of participants
|
|
Cumulative Rate of Improvement in Symptoms of Heartburn
Day 15
|
31.4 percentage of participants
|
48.9 percentage of participants
|
|
Cumulative Rate of Improvement in Symptoms of Heartburn
Day 16
|
34.3 percentage of participants
|
49.7 percentage of participants
|
|
Cumulative Rate of Improvement in Symptoms of Heartburn
Day 17
|
36.3 percentage of participants
|
51.0 percentage of participants
|
|
Cumulative Rate of Improvement in Symptoms of Heartburn
Day 18
|
38.4 percentage of participants
|
54.4 percentage of participants
|
|
Cumulative Rate of Improvement in Symptoms of Heartburn
Day 19
|
40.0 percentage of participants
|
55.7 percentage of participants
|
|
Cumulative Rate of Improvement in Symptoms of Heartburn
Day 20
|
42.7 percentage of participants
|
59.0 percentage of participants
|
|
Cumulative Rate of Improvement in Symptoms of Heartburn
Day 21
|
44.7 percentage of participants
|
59.5 percentage of participants
|
|
Cumulative Rate of Improvement in Symptoms of Heartburn
Day 22
|
48.6 percentage of participants
|
62.7 percentage of participants
|
|
Cumulative Rate of Improvement in Symptoms of Heartburn
Day 23
|
51.3 percentage of participants
|
66.1 percentage of participants
|
|
Cumulative Rate of Improvement in Symptoms of Heartburn
Day 24
|
NA percentage of participants
Data was not collected at this time point.
|
71.3 percentage of participants
|
PRIMARY outcome
Timeframe: Up to Week 4Population: FAS included participants who were randomized and received at least one dose of the study drug.
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.
Outcome measures
| Measure |
Placebo
n=245 Participants
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.
|
TAK-438 10 mg
n=238 Participants
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.
|
|---|---|---|
|
Severity of Symptoms of Heartburn
|
1.140 score on a scale
Interval 0.0 to 2.82
|
1.070 score on a scale
Interval 0.0 to 3.67
|
SECONDARY outcome
Timeframe: Up to Week 4Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=245 Participants
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.
|
TAK-438 10 mg
n=238 Participants
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.
|
|---|---|---|
|
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
Interval 41.4 to 100.0
|
96.00 percentage of days
Interval 46.4 to 100.0
|
|
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
Interval 0.0 to 92.9
|
48.05 percentage of days
Interval 0.0 to 92.9
|
|
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
Interval 3.3 to 100.0
|
81.15 percentage of days
Interval 14.3 to 100.0
|
|
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
Interval 0.0 to 83.3
|
24.15 percentage of days
Interval 0.0 to 84.0
|
SECONDARY outcome
Timeframe: Day 0 to Day 22Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=245 Participants
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.
|
TAK-438 10 mg
n=238 Participants
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.
|
|---|---|---|
|
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
|
78.8 percentage of participants
|
|
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
|
0.0 percentage of participants
|
|
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
|
55.6 percentage of participants
|
|
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
|
58.6 percentage of participants
|
|
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
|
60.6 percentage of participants
|
|
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
|
62.6 percentage of participants
|
|
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
|
67.7 percentage of participants
|
|
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
|
72.7 percentage of participants
|
|
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
|
77.8 percentage of participants
|
|
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
Data was not collected at this time point.
|
80.8 percentage of participants
|
|
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
Data was not collected at this time point.
|
81.8 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
Data was not collected at this time point.
|
83.8 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
|
87.6 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
|
93.8 percentage of participants
|
SECONDARY outcome
Timeframe: Day 0 to Day 24Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=245 Participants
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.
|
TAK-438 10 mg
n=238 Participants
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.
|
|---|---|---|
|
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
|
39.5 percentage of participants
|
|
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
|
0.0 percentage of participants
|
|
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
|
2.2 percentage of participants
|
|
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
Data was not collected at this time point.
|
4.4 percentage of participants
|
|
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
|
8.1 percentage of participants
|
|
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
|
12.6 percentage of participants
|
|
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
|
18.5 percentage of participants
|
|
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
|
22.2 percentage of participants
|
|
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
|
25.2 percentage of participants
|
|
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
|
26.7 percentage of participants
|
|
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
|
28.9 percentage of participants
|
|
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
|
33.3 percentage of participants
|
|
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
|
35.6 percentage of participants
|
|
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
|
38.7 percentage of participants
|
|
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
|
41.7 percentage of participants
|
|
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
|
47.0 percentage of participants
|
|
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
Data was not collected at this time point.
|
55.1 percentage of participants
|
SECONDARY outcome
Timeframe: Day 0 to Day 24Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=245 Participants
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.
|
TAK-438 10 mg
n=238 Participants
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.
|
|---|---|---|
|
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
|
0.0 percentage of participants
|
|
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
|
31.6 percentage of participants
|
|
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
|
33.3 percentage of participants
|
|
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
|
34.5 percentage of participants
|
|
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
|
35.6 percentage of participants
|
|
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
|
38.5 percentage of participants
|
|
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
|
41.4 percentage of participants
|
|
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
|
44.3 percentage of participants
|
|
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
|
44.9 percentage of participants
|
|
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
|
46.0 percentage of participants
|
|
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
Data was not collected at this time point.
|
47.8 percentage of participants
|
|
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
|
51.8 percentage of participants
|
|
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
|
54.1 percentage of participants
|
|
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
|
57.6 percentage of participants
|
|
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
Data was not collected at this time point.
|
58.2 percentage of participants
|
|
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
|
60.0 percentage of participants
|
|
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
|
61.1 percentage of participants
|
|
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
|
62.3 percentage of participants
|
|
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
|
65.2 percentage of participants
|
|
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
|
66.3 percentage of participants
|
|
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
|
69.5 percentage of participants
|
|
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
|
70.1 percentage of participants
|
|
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
|
71.9 percentage of participants
|
|
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
Data was not collected at this time point.
|
74.5 percentage of participants
|
|
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
Data was not collected at this time point.
|
78.7 percentage of participants
|
SECONDARY outcome
Timeframe: Day 0 to Day 24Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=245 Participants
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.
|
TAK-438 10 mg
n=238 Participants
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.
|
|---|---|---|
|
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
|
0.0 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
|
1.6 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
Data was not collected at this time point.
|
4.9 percentage of participants
|
|
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
|
8.2 percentage of participants
|
|
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
|
14.8 percentage of participants
|
|
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
|
18.0 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
Data was not collected at this time point.
|
19.7 percentage of participants
|
|
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
|
24.6 percentage of participants
|
|
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
|
26.2 percentage of participants
|
|
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
|
29.7 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
|
37.0 percentage of participants
|
|
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
|
42.7 percentage of participants
|
|
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
Data was not collected at this time point.
|
50.9 percentage of participants
|
SECONDARY outcome
Timeframe: Up to Week 4Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=245 Participants
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.
|
TAK-438 10 mg
n=238 Participants
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.
|
|---|---|---|
|
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
Interval 0.0 to 1.44
|
0.310 score on a scale
Interval 0.0 to 1.56
|
|
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
Interval 0.25 to 2.82
|
1.420 score on a scale
Interval 0.14 to 2.64
|
|
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
Interval 0.0 to 2.14
|
0.675 score on a scale
Interval 0.0 to 2.04
|
|
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
Interval 0.44 to 2.82
|
1.740 score on a scale
Interval 0.43 to 3.67
|
SECONDARY outcome
Timeframe: Up to Week 4Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=245 Participants
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.
|
TAK-438 10 mg
n=238 Participants
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.
|
|---|---|---|
|
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
Interval 0.0 to 100.0
|
76.70 percentage of days
Interval 0.0 to 100.0
|
|
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
Interval 0.0 to 100.0
|
67.90 percentage of days
Interval 0.0 to 100.0
|
SECONDARY outcome
Timeframe: Day 0 to Day 24Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=245 Participants
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.
|
TAK-438 10 mg
n=238 Participants
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.
|
|---|---|---|
|
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
|
43.5 percentage of participants
|
|
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
|
47.3 percentage of participants
|
|
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
Data was not collected at this time point.
|
51.1 percentage of participants
|
|
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
Data was not collected at this time point.
|
54.8 percentage of participants
|
|
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
Data was not collected at this time point.
|
57.3 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
|
58.6 percentage of participants
|
|
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
|
61.1 percentage of participants
|
|
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
|
63.6 percentage of participants
|
|
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
|
66.3 percentage of participants
|
|
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
|
67.7 percentage of participants
|
|
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
|
73.4 percentage of participants
|
|
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
Data was not collected at this time point.
|
78.7 percentage of participants
|
|
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
Data was not collected at this time point.
|
89.4 percentage of participants
|
|
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
|
0.0 percentage of participants
|
|
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
|
22.2 percentage of participants
|
|
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
Data was not collected at this time point.
|
23.5 percentage of participants
|
|
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
|
24.7 percentage of participants
|
|
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
Data was not collected at this time point.
|
27.2 percentage of participants
|
|
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
|
29.7 percentage of participants
|
|
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
|
32.3 percentage of participants
|
|
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
|
36.0 percentage of participants
|
|
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
|
37.3 percentage of participants
|
|
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
|
41.0 percentage of participants
|
SECONDARY outcome
Timeframe: Day 0 to Day 24Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=245 Participants
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.
|
TAK-438 10 mg
n=238 Participants
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.
|
|---|---|---|
|
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
|
51.0 percentage of participants
|
|
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
|
0.0 percentage of participants
|
|
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
|
23.6 percentage of participants
|
|
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
|
24.9 percentage of participants
|
|
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
Data was not collected at this time point.
|
25.5 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
Data was not collected at this time point.
|
27.5 percentage of participants
|
|
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
Data was not collected at this time point.
|
29.4 percentage of participants
|
|
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
Data was not collected at this time point.
|
30.7 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
Data was not collected at this time point.
|
32.7 percentage of participants
|
|
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
|
35.9 percentage of participants
|
|
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
|
37.9 percentage of participants
|
|
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
|
41.2 percentage of participants
|
|
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
|
42.5 percentage of participants
|
|
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
|
44.4 percentage of participants
|
|
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
|
45.7 percentage of participants
|
|
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
|
47.0 percentage of participants
|
|
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
|
51.6 percentage of participants
|
|
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
|
55.1 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
|
57.1 percentage of participants
|
|
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
|
59.6 percentage of participants
|
|
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
Data was not collected at this time point.
|
63.3 percentage of participants
|
SECONDARY outcome
Timeframe: Up to Week 4Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=245 Participants
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.
|
TAK-438 10 mg
n=238 Participants
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.
|
|---|---|---|
|
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
Interval 0.0 to 2.82
|
0.850 score on a scale
Interval 0.0 to 3.67
|
|
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
Interval 0.0 to 2.54
|
1.110 score on a scale
Interval 0.0 to 2.64
|
SECONDARY outcome
Timeframe: Up to Week 4Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=245 Participants
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.
|
TAK-438 10 mg
n=238 Participants
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.
|
|---|---|---|
|
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
Interval 41.4 to 100.0
|
92.90 percentage of days
Interval 46.4 to 100.0
|
|
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
Interval 0.0 to 92.6
|
53.60 percentage of days
Interval 0.0 to 92.9
|
|
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
Interval 56.0 to 100.0
|
96.40 percentage of days
Interval 59.3 to 100.0
|
|
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
Interval 0.0 to 92.9
|
44.40 percentage of days
Interval 0.0 to 92.9
|
|
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
Interval 3.6 to 100.0
|
79.30 percentage of days
Interval 39.3 to 100.0
|
|
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
Interval 0.0 to 83.3
|
22.95 percentage of days
Interval 0.0 to 84.0
|
|
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
Interval 3.3 to 100.0
|
82.10 percentage of days
Interval 14.3 to 100.0
|
|
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
Interval 0.0 to 78.6
|
25.00 percentage of days
Interval 0.0 to 78.6
|
SECONDARY outcome
Timeframe: Day 0 to Day 22Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=245 Participants
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.
|
TAK-438 10 mg
n=238 Participants
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.
|
|---|---|---|
|
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
|
0.0 percentage of participants
|
|
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
|
46.2 percentage of participants
|
|
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
Data was not collected at this time point.
|
48.7 percentage of participants
|
|
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
|
51.3 percentage of participants
|
|
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
Data was not collected at this time point.
|
56.4 percentage of participants
|
|
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
|
61.5 percentage of participants
|
|
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
|
66.7 percentage of participants
|
|
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
|
74.4 percentage of participants
|
|
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
|
76.9 percentage of participants
|
|
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
Data was not collected at this time point.
|
79.5 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
Data was not collected at this time point.
|
82.9 percentage of participants
|
|
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
|
100.0 percentage of participants
|
SECONDARY outcome
Timeframe: Day 0 to Day 24Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=245 Participants
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.
|
TAK-438 10 mg
n=238 Participants
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.
|
|---|---|---|
|
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
Data was not collected at this time point.
|
81.5 percentage of participants
|
|
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
|
0.0 percentage of participants
|
|
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
|
7.3 percentage of participants
|
|
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
|
9.8 percentage of participants
|
|
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
|
17.1 percentage of participants
|
|
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
Data was not collected at this time point.
|
24.4 percentage of participants
|
|
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
Data was not collected at this time point.
|
31.7 percentage of participants
|
|
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
Data was not collected at this time point.
|
36.6 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
|
39.0 percentage of participants
|
|
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
|
43.9 percentage of participants
|
|
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
|
48.8 percentage of participants
|
|
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
|
51.2 percentage of participants
|
|
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
|
53.8 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
Data was not collected at this time point.
|
63.0 percentage of participants
|
SECONDARY outcome
Timeframe: Day 0 to Day 22Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=245 Participants
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.
|
TAK-438 10 mg
n=238 Participants
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.
|
|---|---|---|
|
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
Data was not collected at this time point.
|
81.7 percentage of participants
|
|
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
|
0.0 percentage of participants
|
|
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
|
61.7 percentage of participants
|
|
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
|
65.0 percentage of participants
|
|
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
Data was not collected at this time point.
|
66.7 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
Data was not collected at this time point.
|
71.7 percentage of participants
|
|
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
Data was not collected at this time point.
|
76.7 percentage of participants
|
|
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
Data was not collected at this time point.
|
80.0 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
Data was not collected at this time point.
|
83.3 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
Data was not collected at this time point.
|
86.7 percentage of participants
|
|
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
|
90.5 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
SECONDARY outcome
Timeframe: Day 0 to Day 24Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=245 Participants
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.
|
TAK-438 10 mg
n=238 Participants
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.
|
|---|---|---|
|
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
|
0.0 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
Data was not collected at this time point.
|
3.2 percentage of participants
|
|
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
|
7.4 percentage of participants
|
|
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
|
10.6 percentage of participants
|
|
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
|
16.0 percentage of participants
|
|
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
|
18.1 percentage of participants
|
|
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
|
20.2 percentage of participants
|
|
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
|
22.3 percentage of participants
|
|
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
|
24.5 percentage of participants
|
|
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
|
28.7 percentage of participants
|
|
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
|
29.8 percentage of participants
|
|
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
|
33.2 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
|
36.4 percentage of participants
|
|
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
|
40.1 percentage of participants
|
|
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
Data was not collected at this time point.
|
45.6 percentage of participants
|
SECONDARY outcome
Timeframe: Day 0 to Day 22Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=245 Participants
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.
|
TAK-438 10 mg
n=238 Participants
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.
|
|---|---|---|
|
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
|
0.0 percentage of participants
|
|
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
|
29.5 percentage of participants
|
|
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
Data was not collected at this time point.
|
31.1 percentage of participants
|
|
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
|
32.8 percentage of participants
|
|
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
Data was not collected at this time point.
|
36.1 percentage of participants
|
|
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
|
39.3 percentage of participants
|
|
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
|
42.6 percentage of participants
|
|
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
|
47.5 percentage of participants
|
|
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
|
49.2 percentage of participants
|
|
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
Data was not collected at this time point.
|
52.5 percentage of participants
|
|
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
|
55.7 percentage of participants
|
|
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
|
59.0 percentage of participants
|
|
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
Data was not collected at this time point.
|
62.3 percentage of participants
|
|
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
Data was not collected at this time point.
|
63.9 percentage of participants
|
|
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
Data was not collected at this time point.
|
67.2 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
|
68.9 percentage of participants
|
|
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
|
72.1 percentage of participants
|
|
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
|
73.8 percentage of participants
|
|
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
Data was not collected at this time point.
|
77.5 percentage of participants
|
|
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
Data was not collected at this time point.
|
79.4 percentage of participants
|
|
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
|
84.5 percentage of participants
|
SECONDARY outcome
Timeframe: Day 0 to Day 24Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=245 Participants
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.
|
TAK-438 10 mg
n=238 Participants
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.
|
|---|---|---|
|
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
|
0.0 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
|
5.3 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
Data was not collected at this time point.
|
10.5 percentage of participants
|
|
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
Data was not collected at this time point.
|
15.8 percentage of participants
|
|
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
Data was not collected at this time point.
|
26.3 percentage of participants
|
|
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
|
31.6 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
|
39.2 percentage of participants
|
|
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
Data was not collected at this time point.
|
59.5 percentage of participants
|
|
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
Data was not collected at this time point.
|
100.0 percentage of participants
|
SECONDARY outcome
Timeframe: Day 0 to Day 24Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=245 Participants
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.
|
TAK-438 10 mg
n=238 Participants
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.
|
|---|---|---|
|
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
|
0.0 percentage of participants
|
|
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
|
32.7 percentage of participants
|
|
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
|
34.5 percentage of participants
|
|
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
Data was not collected at this time point.
|
35.4 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
Data was not collected at this time point.
|
38.1 percentage of participants
|
|
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
Data was not collected at this time point.
|
40.7 percentage of participants
|
|
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
Data was not collected at this time point.
|
42.5 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
Data was not collected at this time point.
|
45.2 percentage of participants
|
|
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
|
49.7 percentage of participants
|
|
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
|
51.5 percentage of participants
|
|
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
|
55.1 percentage of participants
|
|
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
|
56.0 percentage of participants
|
|
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
|
57.8 percentage of participants
|
|
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
|
58.7 percentage of participants
|
|
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
Data was not collected at this time point.
|
61.4 percentage of participants
|
|
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
|
62.3 percentage of participants
|
|
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
|
65.1 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
Data was not collected at this time point.
|
69.0 percentage of participants
|
|
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
Data was not collected at this time point.
|
75.2 percentage of participants
|
SECONDARY outcome
Timeframe: Day 0 to Day 23Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=245 Participants
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.
|
TAK-438 10 mg
n=238 Participants
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.
|
|---|---|---|
|
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
|
0.0 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
Data was not collected at this time point.
|
2.4 percentage of participants
|
|
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
|
4.8 percentage of participants
|
|
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
|
9.5 percentage of participants
|
|
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
|
14.3 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
Data was not collected at this time point.
|
16.7 percentage of participants
|
|
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
|
23.8 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
|
29.1 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
|
36.2 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
SECONDARY outcome
Timeframe: Up to Week 4Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=245 Participants
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.
|
TAK-438 10 mg
n=238 Participants
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.
|
|---|---|---|
|
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
Interval 0.0 to 1.31
|
0.430 score on a scale
Interval 0.0 to 1.56
|
|
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
Interval 0.59 to 2.82
|
1.240 score on a scale
Interval 0.14 to 2.48
|
|
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
Interval 0.0 to 1.44
|
0.280 score on a scale
Interval 0.0 to 1.2
|
|
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
Interval 0.25 to 2.54
|
1.520 score on a scale
Interval 0.14 to 2.64
|
|
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
Interval 0.0 to 2.0
|
0.640 score on a scale
Interval 0.0 to 1.68
|
|
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
Interval 0.6 to 2.82
|
1.695 score on a scale
Interval 0.48 to 3.67
|
|
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
Interval 0.0 to 2.14
|
0.710 score on a scale
Interval 0.0 to 2.04
|
|
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
Interval 0.44 to 2.54
|
1.790 score on a scale
Interval 0.43 to 2.64
|
SECONDARY outcome
Timeframe: Up to Week 4Population: 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.
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 \[anticholinergics or anti-gastrin drugs\].
Outcome measures
| Measure |
Placebo
n=245 Participants
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.
|
TAK-438 10 mg
n=238 Participants
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.
|
|---|---|---|
|
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
Interval 0.0 to 100.0
|
71.40 percentage of days
Interval 0.0 to 100.0
|
|
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
Interval 0.0 to 100.0
|
80.80 percentage of days
Interval 39.3 to 100.0
|
SECONDARY outcome
Timeframe: Up to Week 4Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=245 Participants
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.
|
TAK-438 10 mg
n=238 Participants
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.
|
|---|---|---|
|
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
|
0.0 percentage of participants
|
|
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
|
25.0 percentage of participants
|
|
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
|
26.2 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
|
27.3 percentage of participants
|
|
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
Data was not collected at this time point.
|
28.5 percentage of participants
|
|
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
|
29.6 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
Data was not collected at this time point.
|
30.8 percentage of participants
|
|
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
Data was not collected at this time point.
|
35.4 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
Data was not collected at this time point.
|
41.2 percentage of participants
|
|
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
|
42.3 percentage of participants
|
|
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
|
43.5 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
|
46.9 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
|
49.4 percentage of participants
|
|
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
Data was not collected at this time point.
|
50.8 percentage of participants
|
|
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
|
54.5 percentage of participants
|
|
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
|
61.0 percentage of participants
|
SECONDARY outcome
Timeframe: Up to Week 4Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=245 Participants
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.
|
TAK-438 10 mg
n=238 Participants
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.
|
|---|---|---|
|
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
|
0.0 percentage of participants
|
|
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
|
40.0 percentage of participants
|
|
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
Data was not collected at this time point.
|
60.0 percentage of participants
|
|
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
Data was not collected at this time point.
|
80.0 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
|
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
Data was not collected at this time point.
|
100.0 percentage of participants
|
|
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
|
NA percentage of participants
Data was not collected at this time point.
|
SECONDARY outcome
Timeframe: Up to Week 4Population: 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.
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 \[anticholinergics or anti-gastrin drugs\].
Outcome measures
| Measure |
Placebo
n=245 Participants
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.
|
TAK-438 10 mg
n=238 Participants
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.
|
|---|---|---|
|
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
Interval 0.0 to 2.82
|
1.040 score on a scale
Interval 0.0 to 3.67
|
|
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
Interval 0.0 to 2.0
|
1.030 score on a scale
Interval 0.18 to 1.68
|
Adverse Events
Placebo
Serious events: 1 serious events
Other events: 12 other events
Deaths: 0 deaths
TAK-438 10 mg
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=245 participants at risk
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.
|
TAK-438 10 mg
n=238 participants at risk
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.
|
|---|---|---|
|
Gastrointestinal disorders
Colitis ulcerative
|
0.41%
1/245 • Up to Week 4
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/238 • Up to Week 4
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
Other adverse events
| Measure |
Placebo
n=245 participants at risk
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.
|
TAK-438 10 mg
n=238 participants at risk
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.
|
|---|---|---|
|
Infections and infestations
Viral upper respiratory tract infection
|
4.9%
12/245 • Up to Week 4
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
4.2%
10/238 • Up to Week 4
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
- Publication restrictions are in place
Restriction type: OTHER