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

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)

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.

Study Overview

• Status: Completed
• Conditions: Non-erosive Reflux Disease
• Intervention / Treatment: Drug: Ilaprazole

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 277
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Bundang-gu
    • Seongnam-si, Bundang-gu, Korea, Republic of
      • Seoul National University Bundang Hospital
  • Busanjin-gu
    • Busan, Busanjin-gu, Korea, Republic of
      • Inje University Busan Paik Hospital
  • Dongjak-gu
    • Seoul, Dongjak-gu, Korea, Republic of
      • Seoul Metropolitan Government Seoul National University Boramae Medical Center
  • Jeonju-si
    • Jeonju, Jeonju-si, Korea, Republic of
      • Chonbuk National University Hospital
  • Jongno-gu
    • Seoul, Jongno-gu, Korea, Republic of
      • Kangbuk Samsung Hospital, Sungkyunkwan University
    • Seoul, Jongno-gu, Korea, Republic of
      • Seoul National University Hospital
  • Jung-gu
    • Seoul, Jung-gu, Korea, Republic of
      • Inje University Seoul Paik Hospital
  • Seodaemun-gu
    • Seoul, Seodaemun-gu, Korea, Republic of
      • Severance Hospital Yonsei University Health System
  • Songpa-gu
    • Seoul, Songpa-gu, Korea, Republic of
      • Asan Medical Center
  • Wonmi-gu
    • Bucheon, Wonmi-gu, Korea, Republic of
      • Soon Chun Hyang University Hospital, Buchon
  • Yangcheon-gu
    • Seoul, Yangcheon-gu, Korea, Republic of
      • Ewha Womans University Mokdong Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female aged ≥ 19 years and ≤ 80 years

2. 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

3. Voluntarily provide written informed consent to participate in this study

Exclusion Criteria:

1. Esophageal stenosis, ulcerative stenosis, esophagogastric varices or Barrett esophagus confirmed by past upper gastrointestinal endoscopy within 1 year prior to screening
2. Active peptic ulcer or gastrointestinal bleeding confirmed by past upper gastrointestinal endoscopy at screening or within 4 weeks prior to screening

3. 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

4. Clinically significant abnormal findings on ECG (major arrhythmia, multifocal PVC, second-degree or higher AV block, etc.) within 3 months prior to screening
5. 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
6. Expected to continuously take nonsteroidal antiinflammatory drugs (NSAIDs) including aspirin or steroid preparations during the study
7. 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
8. Zollinger-Ellison syndrome; past history of alcoholism or drug abuse
9. Past history of allergic symptoms (rash, fever, pruritus, etc.) or hypersensitivity to any ingredient of the Investigational product
10. 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)
11. Pregnant or nursing women
12. Women of childbearing potential who do not use proper contraception during the study
13. Active liver disease; ALT or AST > ULN x 2 at screening; or history of hepatic encephalopathy, esophageal varix, or portacaval shunt
14. Receiving renal dialysis or history of kidney transplantation or presence of severe renal impairment (stage 4 or 5 chronic renal disease)
15. Participated in another clinical study and took an investigational product within 3 months prior to screening
16. Considered by the investigator to be ineligible to participate in this study for other reasons

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment Group; 10mg Ilaprazole x 2 tablets	Drug: Ilaprazole; 10mgx2 tablet once daily for weeks; Other Names: IY81149
Placebo Comparator: Control Group; 10mg placebo of Ilaprazole x 2 tablets	Drug: Ilaprazole; 10mgx2 tablet once daily for weeks; Other Names: IY81149

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Il-Yang Pharm. Co., Ltd.
• Investigators: Principal Investigator: DongHo Lee, MD.PhD, Seoul National University Bundang Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2018
• Primary Completion (Actual): February 25, 2020
• Study Completion (Actual): February 25, 2020

Study Registration Dates

• First Submitted: February 19, 2018
• First Submitted That Met QC Criteria: February 19, 2018
• First Posted (Actual): February 23, 2018

Study Record Updates

• Last Update Posted (Actual): January 5, 2021
• Last Update Submitted That Met QC Criteria: December 30, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: PPI; NERD; Ilaprazole
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastroesophageal Reflux
• Other Study ID Numbers: IL49NE03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: IPD will not be shared to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No