Phase III Study to Evaluate Safety and Efficacy of Ilaprazole in Patients With NERD

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of Ilaprazole 20 mg in patients with non-erosive reflux disease. This study intends to demonstrate the clinical superiority of Ilaprazole 20 mg to placebo administered once daily for 4 weeks.

Detailed Description
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This study is multicenter, randomized, parallel, double blind, placebo-controlled phase III study

Official Title
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A Multicenter, Randomized, Parallel, Double Blind, Placebo-controlled Phase III Study to Evaluate Safety and Efficacy of Ilaprazole 20mg in Patients With Non-erosive Reflux Disease(NERD)

Conditions
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Non-erosive Reflux Disease

Intervention / Treatment
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* Drug: Ilaprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged ≥ 19 years and ≤ 80 years Diagnosed with non-erosive reflux disease meeting all of the following criteria: 2-1) At least either heartburn or acid regurgitation has persisted for at least past 3 months before screening 2-2) Have experienced at least either heartburn or acid regurgitation of moderate or higher intensity on at least 2 days of 7 days prior to initiation of the investigational product 2-3) Esophageal mucosal breaks by LA Classification are not observed on upper gastrointestinal endoscopy at screening Voluntarily provide written informed consent to participate in this study Exclusion Criteria: Esophageal stenosis, ulcerative stenosis, esophagogastric varices or Barrett esophagus confirmed by past upper gastrointestinal endoscopy within 1 year prior to screening Active peptic ulcer or gastrointestinal bleeding confirmed by past upper gastrointestinal endoscopy at screening or within 4 weeks prior to screening Abnormal value on laboratory test at screening: 3-1) Total Bilirubin, Creatinine > Upper limit of normal (ULN) x 1.5 3-2) Alkaline Phosphatase, BUN > ULN x 2 Clinically significant abnormal findings on ECG (major arrhythmia, multifocal PVC, second-degree or higher AV block, etc.) within 3 months prior to screening Have taken H2 receptor antagonists (H2RA), prostaglandin preparations, mucosal protective drugs, prokinetics, etc. within 2 weeks prior to initiation of the investigational product administration, or has taken PPIs within 4 weeks prior to initiation of the investigational product administration Expected to continuously take nonsteroidal antiinflammatory drugs (NSAIDs) including aspirin or steroid preparations during the study Surgical or medical condition that may significantly influence the absorption, distribution, metabolism or excretion of drug, including but not limited to: history of major gastrointestinal surgery such as gastrectomy, gastroenterostomy, colectomy, gastric bypass, gastric ligation or gastric banding; presence or history of active inflammatory bowel disease within 12 months prior to screening; has undergone critical surgery that may influence gastric acid secretion with exception of surgeries such as appendectomy, cholecystectomy, and hysterectomy Zollinger-Ellison syndrome; past history of alcoholism or drug abuse Past history of allergic symptoms (rash, fever, pruritus, etc.) or hypersensitivity to any ingredient of the Investigational product Past history of treated or untreated malignancy, with or without local recurrence or metastasis, within 5 years prior to screening (with exception of local basal cell carcinoma of skin) Pregnant or nursing women Women of childbearing potential who do not use proper contraception during the study Active liver disease; ALT or AST > ULN x 2 at screening; or history of hepatic encephalopathy, esophageal varix, or portacaval shunt Receiving renal dialysis or history of kidney transplantation or presence of severe renal impairment (stage 4 or 5 chronic renal disease) Participated in another clinical study and took an investigational product within 3 months prior to screening Considered by the investigator to be ineligible to participate in this study for other reasons

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A mulicenter, randomized, parallel, double blind, placebo-controlled
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment Group<br>10mg Ilaprazole x 2 tablets | Drug: Ilaprazole<br>* 10mgx2 tablet once daily for weeks<br>* Other names: IY81149;|
| Placebo Comparator: Control Group<br>10mg placebo of Ilaprazole x 2 tablets | Drug: Ilaprazole<br>* 10mgx2 tablet once daily for weeks<br>* Other names: IY81149;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of loss of esophagitis symptom at 4 weeks of treatment vs pre-dose | Percentage of subjects who were assessed as having 'lost' the frequency and intensity of typical esophagitis symptoms by RDQ assessment at 4 weeks of treatment | 4 weeks(28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chang in esophagitis symptom score at 4 weeks of treatment vs pre-dose | The mean scores for esophagitis symptom (heartburn and/or acid regurgitation) frequency and intensity assessed with RDQ (Questions a, b/c, d) and the change in mean score across both domains. | 4 weeks(28 days) | 
| Change in PAGI-QoL score at 4 weeks of treatment vs pre-dose | The change in mean score for quality of life assessed with PAGI-QoL | 4 weeks(28 days) | 
| Change in esophagitis symptom score according to the maximum number of rescue medication doses per day | The mean scores for esophagitis symptom (heartburn and/or acid regurgitation) frequency and intensity assessed with RDQ (Questions a, b/c, d) at 4 weeks of treatment versus pre-dose according to the maximum number of rescue medication doses per day and the change in mean score across both domains. | 4 weeks(28 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NERD, PPI, Ilaprazole