TAK-438

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.

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).

An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product; it did not necessarily have to have a causal relationship with this treatment. The different categories of intensity (severity) were characterized as follows: Mild: The AE was transient and easily tolerated by the participant. Moderate: The AE caused the participant discomfort and interrupted the participant's usual activities. Severe: The AE caused considerable interference with the participant's usual activities.

Vital signs included blood pressure, pulse, respiratory rate, and body temperature (armpit).

The investigator or the subinvestigator interpreted the ECG using 1 of the following categories: "within normal limits", "abnormal but not clinically significant", or "abnormal and clinically significant". The time that the ECG was performed was recorded. The following parameters were recorded from the participant's ECG trace: heart rate, RR interval, PR interval, QT interval, QRS duration, and QTc interval.

Laboratory tests for hematology, biochemistry, and urinalysis were be performed.

AUC(0-tau) is a measure of the area under the plasma concentration-time curve from the time 0 to time tau over a dosing interval, where tau is the length of the dosing interval, 24 hours, calculated using the linear trapezoidal rule.

AUC(0-tlqc) is a measure of the area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration, calculated using the linear trapezoidal rule.

AUMC(0-tlqc) is a measure of the area under the first moment plasma concentration-time curve from time 0 to time of the last quantifiable concentration (tlqc), calculated using the linear trapezoidal rule.

MRT(0-tlqc) is a measure of the mean residence time from time 0 to time of the last quantifiable concentration (tlqc) calculated as MRT(0-tlqc)=AUMC(0-tlqc)/AUC(0-tlqc).

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

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

AUC(0-inf) is a measure of the area under the plasma concentration-time curve from time 0 to infinity.

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.

AUMC(0-inf) is a measure of the area under the first moment plasma concentration-time curve from time 0 to infinity.

Mean residence time, calculated as MRT=AUMC(0-inf)/AUC(0-inf)

The cumulative urinary excretion ratio is defined as the percentage of the dose excreted in the urine.

(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.

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

(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.

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.

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.

Using a calibrated gastric pH monitor, the measurement of stomach pH will be made continuously over a 24-hour period at Baseline and over a 96-hour period following the administration of study drug.

Using a calibrated gastric pH monitor, the measurement of stomach pH will be made continuously over a 24-hour period at Baseline and over a 24-hour period following the administration of study drug.

Using a calibrated gastric pH monitor, the measurement of stomach pH will be made continuously over a 24-hour period at Baseline and over a 24-hour period following the administration of study drug.

Using a calibrated gastric pH monitor, the measurement of stomach pH will be made continuously over a 12-hour period at Baseline and over a 12-hour period following the administration of study drug.

Using a calibrated gastric pH monitor, the measurement of stomach pH will be made continuously over a 12-hour period at Baseline and over a 12-hour period following the administration of study drug.

Using a calibrated gastric pH monitor, the measurement of stomach pH will be made continuously over a 24-hour period at Baseline and over a 96-hour period following the administration of study drug.

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 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug.

AUC(0-48) is a measure of the area under the plasma concentration-time curve from time 0 to 48 hours, calculated using the linear trapezoidal rule.

AUMC(0-tlqc) is a measure of the area under the first moment plasma concentration-time curve from time 0 to time of the last quantifiable concentration (tlqc), calculated using the linear trapezoidal rule.

MRT(0-tlqc) is a measure of the mean residence time from time 0 to time of the last quantifiable concentration (tlqc) calculated as MRT(0-tlqc)=AUMC(0-tlqc)/AUC(0-tlqc).

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

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

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

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.

AUMC(0-inf) is a measure of the area under the first moment plasma concentration-time curve from time 0 to infinity, calculated as AUMC(0-tlqc) + lqc x tlqc/λz + lqc/λz\^2.

Mean residence time, calculated as MRT=AUMC(0-inf)/AUC(0-inf).

The cumulative urinary excretion ratio is defined as the percentage of the dose excreted in the urine.