Ilaprazole for the Treatment of Duodenal Ulcer in Chinese Patients (Phase 2)

Efficacy and Safety of Ilaprazole for Acute Duodenal Ulcer: A Randomized,Double-Blind,Omeprazole-Controlled,Multicenter,and Phase2 Trial in China

Patients with endoscopically diagnosed active duodenal ulcer disease were enrolled in a randomized, double-blind, parallel and dose-ranging trial. They were randomly assigned into four groups to be treated for up to four weeks and be seen at week 1, 2 and 4: three of ilaprazole, 5, 10, and 20 mg/day, and one of omeprazole 20 mg/day as positive control. The primary endpoint was the ulcer healing rate at week 4. Healing of ulcer was determined by its resolution from active to scarring stage. Symptoms relief was evaluated as secondary end points by using a graded score. Safety and tolerability were evaluated on basis of clinical assessments.

Study Overview

• Status: Completed
• Conditions: Duodenal Ulcer
• Intervention / Treatment: Drug: 10 mg ilaprazole; Drug: 5 mg ilaprazole; Drug: 20 mg ilaprazole; Drug: 20 mg omeprazole

Detailed Description

The primary endpoint was the healing rate of ulcers, which based on post-treatment (week 4) endoscopic changes in stage of the ulcer relative to baseline (week 0) levels. Stages of the ulcers were endoscopically assessed according to the degree of ulceration, regenerating epithelialization, and scarring, which was defined as follows: A stage (active stage, A1 & A2) where A1 stage is more severe than A2 stage, H stage (healing stage, H1 & H2) where H2 stage is better than H1 stage, and S stage (scarring stage, S1 (red scar) & S2 (white scar)) where S stage is the best stage in the three stages and S2 stage is better than S1.Healing of ulcer is deemed successful if an ulcer in A stage resolved to S stage at the end of the treatment period, regardless of S1 or S2. When endoscopy demonstrated successful ulcer healing, study medication was discontinued. Patients returned at week 2, and if unhealed further endoscopic assessment would be done at week 4. Secondary endpoints included post-treatment resolution of related gastrointestinal symptoms such as upper abdominal pain, heartburn, acid regurgitation, nausea & vomiting, eructation, and increased flatus. These symptoms were recorded on a scale ranging from 0 to 3(0=none, 1=mild, 2=moderate, 3=severe) at baseline, week 1, 2, and 4. Resolution of symptoms were defined as "excellence", "effective", "improved", or "ineffective" relative to baseline levels, of which complete symptom relief or complete absence of the symptom without recurrence was deemed as "excellence". Safety assessments based mainly on the occurrence, frequency, and severity of adverse events, which were monitored throughout the duration of the study, and also based on comprehensive indexes, including physical examination, electrocardiography, and routine laboratory investigations, which were performed at baseline and repeated at the end of the treatment period. For all adverse events, where necessary, patients were withdrawn from the study.

• Study Type: Interventional
• Enrollment (Actual): 235
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Peking University Third Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Consenting patients were eligible for enrollment if they:

  1. were 18-65 years of age,
  2. had endoscopically diagnosed active duodenal ulcers within the previous 72 hours,
  3. the number of ulcers was at least one, but no more than two with the larger diameter 0.3-2.0cm.

Exclusion Criteria:

• Patients were ineligible if they:

  1. had cancerous or complex ulcers, Zollinger-Ellison syndrome, esophageal erosion or ulcer, varices of esophagus or fundus of stomach, or pyloric stenosis,
  2. had a known history of gastric acid suppression operation, esophageal operation or peptic operation other than simple closure of perforation,
  3. had severe complications (e.g., pyloric obstruction, active bleeding under endoscope), severe other diseases of digestive tract such as Crohn's disease and ulcerative colitis, and severe other systemic diseases,
  4. were female patients who were breast feeding, pregnant, or intended to become pregnant during the study,
  5. had taken proton pump inhibitors within the 5 days or for more than three consecutive days within the two weeks immediately preceding start of study drug,
  6. participated in a clinical trial with an investigational drug or device within the past three months,
  7. had hypersensitivity or idiosyncratic reaction to omeprazole or any other benzimidazole,
  8. had alcoholic intemperance, drug addiction or any other improper habits.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 10 mg ilaprazole	Drug: 10 mg ilaprazole; Two 5-mg ilaprazole tablets (Livzon Pharm Group Inc., China) together with two placebo tablets and one placebo capsule in a package being taken orally each morning on an empty stomach for 4 weeks
Experimental: 5 mg ilaprazole	Drug: 5 mg ilaprazole; One 5-mg ilaprazole tablet (Livzon Pharm Group Inc., China) together with three placebo tablets and one placebo capsule in a package being taken orally each morning on an empty stomach for 4 weeks
Experimental: 20 mg ilaprazole	Drug: 20 mg ilaprazole; Four 5-mg ilaprazole tablets together with one placebo capsule in a package being taken orally each morning on an empty stomach for 4 weeks
Active Comparator: 20 mg omeprazole	Drug: 20 mg omeprazole; One 20-mg omeprazole capsule (AstraZeneca, Losec) together with four placebo tablets in a package being taken orally each morning on an empty stomach for 4 weeks; Other Names: Losec,AstraZeneca

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary endpoint was the healing rate of ulcers, which based on post-treatment (week 4) endoscopic changes in stage of the ulcer relative to baseline (week 0) levels.	week 4

Secondary Outcome Measures

Outcome Measure	Time Frame
Secondary endpoints included post-treatment resolution of related gastrointestinal symptoms such as upper abdominal pain, heartburn, acid regurgitation, nausea & vomiting, eructation, and increased flatus.	week 4

Collaborators and Investigators

• Sponsor: Livzon Pharmaceutical Group Inc.
• Investigators: Principal Investigator: S R Lin, M.D, Peking University Third Hospital

Publications and helpful links

General Publications

• Wang L, Zhou L, Lin S, Hu H, Xia J. A new PPI, ilaprazole compared with omeprazole in the treatment of duodenal ulcer: a randomized double-blind multicenter trial. J Clin Gastroenterol. 2011 Apr;45(4):322-9. doi: 10.1097/MCG.0b013e3181e88515.

Study record dates

Study Major Dates

• Study Start: October 1, 2004
• Primary Completion (Actual): March 1, 2005
• Study Completion (Actual): May 1, 2005

Study Registration Dates

• First Submitted: August 1, 2009
• First Submitted That Met QC Criteria: August 5, 2009
• First Posted (Estimate): August 6, 2009

Study Record Updates

• Last Update Posted (Estimate): August 6, 2009
• Last Update Submitted That Met QC Criteria: August 5, 2009
• Last Verified: August 1, 2009

More Information

Terms related to this study

• Keywords: Randomized trial; Duodenal ulcer; Proton pump inhibitor; Ilaprazole; Acid suppression
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Stomach Diseases; Intestinal Diseases; Peptic Ulcer; Duodenal Diseases; Ulcer; Duodenal Ulcer; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Omeprazole
• Other Study ID Numbers: Livzon-IY-81149-01; 2004L00137