A Study in Patients With Erosive Esophagitis to Investigate Safety, Tolerability, and Healing Rates After 4 Weeks Treatment of X842 or Lansoprazole and Symptom Pattern During Subsequent 4 Weeks Treatment With Lansoprazole

The healing of erosive esophagitis due to gastro-esophageal reflux disease (GERD) was assessed. It supported the dose selection X842,through the assessment of healing of erosive esophagitis due to GERD based on endoscopic assessment after 4 weeks of treatment. The dose that would lead to having 85% of the patients have esophageal mucosa healing after 4 weeks of treatment. Following the endoscopic evaluation, all patients received subsequent 4 weeks of open-label treatment with lansoprazole. Repeated symptom evaluation was assessed during this period to detect the symptom pattern. Endoscopy evaluation at 4 weeks was based on the level and duration of acid control achieved with X842. Symptom evaluation was assessed using the validated patient-reported outcome (PRO) QOLRAD (Heartburn version) and patient diaries (RESQ-eDiary).

Time frame: Week 4

Population: The FAS consisted of all patients who had been randomized and received at least 1 dose of study drug. FAS erosive is a subset of FAS consisted of patients who had been classified as erosive (Grade A, B, C or D) as screening according to the central reading or imputed by local reading if missing.

Reflux-related symptom pattern was evaluated during initial 4 weeks of treatment with 4 dose levels of X842 and with Lansoprazole, and symptom pattern during subsequent additional 4 weeks of open-label treatment with Lansoprazole. Heartburn version of QOLRAD is a disease-specific instrument containing 25 questions addressing concerns associated with gastrointestinal symptoms. Questions were rated on a seven-grade (1-7) Likert scale, where a score of 1 represented low quality of life, and as score increased, the patient's condition was considered better. Questions were categorized into 5 domains: emotional distress, sleep disturbance, vitality, food/drink problems, and physical/social functioning. The score in each domain was calculated as the mean of all items in that domain. The score ranges from 1 to 175, higher scores mean a better outcome. After endoscopic evaluation, patients received lansoprazole and underwent symptom evaluation using validated PRO QOLRAD and patient diaries.

Time frame: Baseline, Weeks 1, and 8

Population: The FAS consisted of all patients who had been randomized and received at least 1 dose of study drug. Here, the Number Analyzed in the table represents the count of patients who were measured and analyzed for the specific Outcome Measure during the given week.

Investigator assessed severity and frequency of patients' heartburn, regurgitation, and dysphagia in 7 days. Assessment included both severity grade (for severity, items were coded: none, mild, moderate, severe where none represented no complaints, severe represented incapacitating symptoms) and frequency (for frequency, a 7-graded Likert scale was used, ranging from none to all of time) of symptoms. Symptoms were scored as follows: none (no complaints), mild (aware of symptom, but easily tolerated), moderate (discomforting symptom, sufficient to cause interference with normal daily activities and/or sleep), severe (incapacitating symptom, with inability to perform normal daily activities and/or sleep). Following endoscopic evaluation, patients received lansoprazole and underwent symptom evaluation using validated PRO QOLRAD (Heartburn version) and patient diaries.Here, for frequency- All of the time and None of the time, and for symptoms- none and severe data has been presented.

Time frame: Weeks 1 and 8

Population: The FAS consisted of all patients who had been randomized and received at least 1 dose of the study drug. Here, the Number Analyzed in the table represents the count of patients who were measured and analyzed for the specific Outcome Measure during the given week.

The safety and tolerability of the four dose levels of X842 and Lansoprazole were evaluated, where Lansoprazole served as the active comparator. Here TEAE- Treatment-emergent adverse event, ADR- Adverse drug reaction, SAE- Serious adverse event, and AESI- Adverse events of special interest.

Time frame: From Screening (Day -7 to Day 0) until Week 8

Population: The safety analysis set consisted of all patients who had been randomized and received at least 1 dose of study drug. Patients were analyzed according to the treatment actually received.

Heartburn with at most mild symptoms in a 24-hour day was defined as a day where the patient reported having either no symptoms, very mild symptoms, or mild burning feeling or pain behind the breast or in the center of the upper stomach (score between 0-2) for both morning and evening. Heartburn assessed the severity as per the following scores (0=Did not have, 1=Very mild, 2=Mild, 3=Moderate, 4=Moderately severe, 5=Severe). Here higher scores represent the worst outcome, whereas lower scores represent the better outcome. After endoscopic evaluation, patients received lansoprazole, and symptom evaluation was conducted to detect patterns. Endoscopy evaluation at 4 weeks was based on the level and duration of acid control achieved with X842. Symptom evaluation involved the use of validated PRO QOLRAD (Heartburn version) and patient diaries.

Time frame: Weeks 1 and 8

Population: The FAS consisted of all patients who had been randomized and received at least 1 dose of the study drug. Here, the Number Analyzed in the table represents the count of patients who were measured and analyzed for the specific Outcome Measure during the given week.

Heartburn-free in a 24-hour day was a day where patient reported having no burning feeling or pain behind breast or in center of upper stomach for both morning and evening. Percentage of heartburn-free 24-hour days based on eDiary(Reflux Symptom Questionnaire electronic Diary: RESQ-eDiary) was evaluated. Reflux-related symptom pattern was evaluated during initial 4 weeks of treatment with four dose levels of X842 and with Lansoprazole, and symptom pattern during subsequent additional 4 weeks Lansoprazole treatment in open-label. Modified RESQ-eDiary was validated self-reported questionnaire electronic symptom diary. mRESQ-eD has 3 domains \[i.e. Heartburn (min-max: 0-10), Other GERD signs/symptoms (min-max:0-15) and Regurgitations/Reflux (min-max: 0-8)\]. Endoscopy followed by lansoprazole administration and symptom evaluation using PRO QOLRAD (Heartburn version) and patient diaries assessed acid control achieved with X842 at 4 weeks.

Time frame: Weeks 1 and 8

Population: The FAS consisted of all patients who had been randomized and received at least 1 dose of the study drug. Here, the Number Analyzed in the table represents the count of patients who were measured and analyzed for the specific Outcome Measure during the given week.