TAK-438

HP infection status was determined by \^13C Urea Breath Test (\^13C-UBT). The urea breath test is used to detect infection with HP, a bacteria associated with stomach ulcers, by testing individual breath samples in a central laboratory. The percentages are rounded off to report the nearest ten.

Endoscopic healing was defined as the disappearance of all white coats associated with GUs confirmed endoscopically.

Endoscopic healing was defined as the disappearance of all white coats associated with duodenal ulcers as confirmed endoscopically.

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.

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.

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.

Erosive esophagitis recurrence is defined as participants endoscopically confirmed to have erosive esophagitis (Los Angeles \[LA\] classification grades A to D) during the Maintenance Phase (24 weeks). Grade A: \>/=1 mucosal breaks \</=5 mm, none of which extends between the tops of the mucosal folds; Grade B: \>/=1 mucosal breaks \>5 mm, none of which extends between the tops of two mucosal folds; Grade C: mucosal breaks that extend between the tops of two or more mucosal folds, but which involve \<75% of esophageal circumference; Grade D: mucosal breaks which involve \>/=75% of esophageal circumference.

Endoscopic healing is defined as participants endoscopically diagnosed as Los Angeles classification grade O during the treatment phase. Grade O indicates there are no mucosal breaks in the mucosa.

Gastric and esophageal pH4 HTR (pH 4 Holding Time Ratio) will be calculated based on 24-hour gastroesophageal pH monitoring.

Treatment-emergent adverse events are defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through the last visit of study.

The participants are judged to be H. pylori-negative or H. pylori-positive based on the 13C-Urea Breath Test.

Heartburn symptoms will be collected by participant diaries.

Heartburn symptoms will be collected by participant diaries.

Heartburn symptoms will be collected by participant diaries.

Endoscopic healing rate : Rate of participants who have endoscopically confirmed all of the white coatings disappeared.

Endoscopic recurrence of erosive esophagitis is defined as those participants who have endoscopically confirmed EE of Grade A to D as defined by the Los Angeles (LA) Classification Grading System. The definitions of each grade are: Grade O (No mucosal break), Grade A (Mucosal break \<5 mm), Grade B (Mucosal break ≥5 mm), Grade C (Mucosal break continuous between two or more folds and \<75% of the circumference) and Grade D (Mucosal break ≥75% of the circumference).

Mucosal defects with a white coating of 3 mm or larger will be determined as ulcers. Recurrence rate of gastric or duodenal ulcer within 24 weeks will be calculated for each treatment group.

Endoscopic healing rate : Rate of participants who have endoscopically confirmed all of the white coatings disappeared.

Endoscopic healing of erosive esophagitis is defined as those participants who have endoscopically confirmed EE of Grade O as defined by the Los Angeles (LA) Classification Grading System. The definitions of each grade are: Grade O (No mucosal break), Grade A (Mucosal break \<5 mm), Grade B (Mucosal break ≥5 mm), Grade C (Mucosal break continuous between two or more folds and \<75% of the circumference) and Grade D (Mucosal break ≥75% of the circumference).

Participants used the Reflux Symptom Questionnaire Electronic Diary (RESQ-eD) every morning upon waking and every evening before going to sleep to document the presence of daytime and nighttime heartburn and regurgitation. The percentage of heartburn-free (HBF) 24-hour periods was calculated for each participant using the following formula: (total 24-hour periods that are heartburn free / total 24-hour periods for which both a daytime and nighttime result is marked) x 100%.

(AUC(0-tlqc) is a measure of total plasma exposure to the drug from time 0 to time of the last quantifiable concentration (AUC\[0-tlqc\]).

AUC(0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity.

AUC(0-tau) is a measure of the area under the plasma concentration-time curve from time 0 to time tau over a dosing interval, where tau is the length of the dosing interval.

Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.

(Cmax-Cmin)/Cavg, where Cmin is the minimum observed plasma concentration and Cavg is the average plasma concentration at steady state.

Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax.

Terminal elimination rate constant (λz) is the rate at which drugs are eliminated from the body.

Terminal Phase Elimination Half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.

CL/F is apparent clearance of the drug from the plasma, calculated as the drug dose divided AUC(0-24), expressed in L/hr.

Vz/F is the distribution of a drug between plasma and the rest of the body following oral administration, calculated as CL/F divided by λz.

Ae(0-t) is the total amount of drug excreted in urine from time 0 to t, where t is 24 hours on Day 1 and 48 hours on Day 7.

Ae(0-tau) is the total amount of drug excreted in urine from time 0 to tau, where tau equals 24 hours.

CLr is a measure of apparent clearance of the drug from the urine calculated as total amount excreted in the urine from time 0 to 24 hours postdose / plasma area under the curve from time 0 to 24 hours post-dose.

Fe is a measure of the fraction of drug excreted in urine and is calculated as Fe = (total amount excreted in the urine from time 0 to 24 hours post-dose / dose)×100.

A baseline physical examination (defined as the pretreatment assessment immediately prior to the start of study drug) will consist of the following body systems: (1) eyes; (2) ears, nose, throat; (3) cardiovascular system; (4) respiratory system; (5) gastrointestinal system; (6) dermatologic system; (7) extremities; (8) musculoskeletal system; (9) nervous system; (10) lymph nodes; (11) genitourinary system; and (12) other. All subsequent physical examinations should assess clinically significant changes from the baseline examination.

Participants with at least one potentially clinically significant post-baseline vital sign finding. Vital signs will include body temperature (oral temperature), sitting blood pressure (after sitting for 5 minutes), and pulse (bpm).

Full 12-lead ECGs will be recorded using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT (using Bazett correction; QTcB) intervals. The investigator or other qualified physician will interpret each ECG using one of the following categories: within normal limits, abnormal but not clinically significant, or abnormal and clinically significant.

Laboratory tests for hematology, serum chemistries, coagulation tests, and urinalysis will be performed.

Treatment-emergent adverse events are defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 7 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug.

Assessed by physical examination, ECG, and safety tests of blood/urine

Assessed by adverse events

Primary pharmacokinetic parameters (AUC (0-tlqc), AUC (0-inf), Cmax) for TAK-438 and its metabolites M-I, M-II, M-III and M-IV-Sul will be subject to statistical analysis