Efficacy and Safety of Dexlansoprazole in Healing and Maintaining Healing of Erosive Esophagitis

A Phase 3 Study to Evaluate the Efficacy and Safety of Dexlansoprazole (60 mg QD) and an Active Comparator, Lansoprazole (30 mg QD) on Healing of Erosive Esophagitis, and Maintenance of Healing in Subjects With Healed Erosive Esophagitis With Dexlansoprazole (30 mg QD) and Placebo

The purpose of this study is to determine the efficacy of dexlansoprazole compared to lansoprazole in healing erosive esophagitis (EE) in Chinese participants.

Study Overview

• Status: Terminated
• Conditions: Erosive Esophagitis
• Intervention / Treatment: Drug: Dexlansoprazole; Drug: Lansoprazole; Drug: Placebo

Detailed Description

The drug being tested in this study is called dexlansoprazole. Dexlansoprazole is being tested to treat people who have EE. This study will look at erosive esophageal healing in people who take dexlansoprazole.

The study will enroll approximately 450 participants. Participants will be randomly assigned to one of the two treatment groups with 1:1 ratio-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

• Dexlansoprazole 60 mg
• Lansoprazole 30 mg

After 8 weeks of treatment, participants will be evaluated to assess esophageal healing. If the EE is healed participants will be randomly assigned to one of two different treatment groups with 1:1 ratio:

• Dexlansoprazole 30 mg
• Placebo (dummy inactive pill) - this is a capsule that looks like the study drug but has no active ingredient.

All participants will be asked to take one capsule at the same time each day throughout the study.

This multi-center trial will be conducted in China. The overall time to participate in this study is up to 39 weeks. Participants will make 7 visits to the clinic, and will be contacted by telephone 5 to 10 days after last dose of study drug for a follow-up assessment.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Peking Union Medical College Hospital
    • Beijing, Beijing, China, 100032
      • Peking University First Hospital
  • Chong Qing
    • Chong Qing, Chong Qing, China, 404100
      • Chongqing Three Gorges Central Hospital
  • Fu Jian
    • Xia Men, Fu Jian, China, 361004
      • Zhongshan Hospital Xiamen University
  • Guang XI
    • Nan Ning, Guang XI, China, 530022
      • The people's hospital of Guangxi Zhuang Autonomous Region
  • Gui Lin
    • Hai Kou, Gui Lin, China, 570100
      • Affilicated Hospital of Guilin Medical University
  • Hebei
    • Shijiazhuang, Hebei, China, 050051
      • Hebei General Hospital
  • Hu Bei
    • Shi Yan, Hu Bei, China, 442000
      • Taihe Hospital
    • Wuhan, Hu Bei, China, 430000
      • Central Hospital of Wuhan
    • Wuhan, Hu Bei, China, 430000
      • Puai Hospital Of Wuhan City
  • Hu Nan
    • Chang Sha, Hu Nan, China, 410015
      • The Third Hospital of Changsha
  • Jiang Su
    • Nan Jing, Jiang Su, China, 210009
      • Zhongda Hospital Southeast
    • Wu XI, Jiang Su, China, 212001
      • Affiliated Hospital of Jiangsu University
    • Wu XI, Jiang Su, China, 214023
      • Wuxi People's Hospital
  • Jilin
    • Changchun, Jilin, China, 130000
      • The First Hospital of Jilin University
  • Liaoning
    • Shenyang, Liaoning, China, 110004
      • Shengjing Hospital of China Medical University
  • Shandong
    • Binzhou, Shandong, China, 256603
      • Binzhou Medical University Hospital
    • Jinan, Shandong, China, 250013
      • Jinan Central Hospital
    • Liaocheng, Shandong, China, 252000
      • Liaocheng Hospital
    • Qingdao, Shandong, China, 266003
      • The Affiliated Hospital of Qingdao University
  • Shanghai
    • Shanghai, Shanghai, China, 20001
      • Renji Hospital Shanghai Jiaotong University School of Medicine
  • Shanxi
    • Taiyuan, Shanxi, China, 030001
      • The First Hospital of Shanxi Medical University
    • Taiyuan, Shanxi, China, 030001
      • The Second Hospital of Shanxi Medical University
  • Si Chuang
    • Cheng Du, Si Chuang, China, 610041
      • West China Hospital,Sichuan University
  • Tianjin
    • Tianjin, Tianjin, China, 300121
      • Tianjin People's Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Has endoscopically confirmed EE as defined by the LA Classification Grading System (A-D).

Exclusion Criteria:

1. Participant is required to take excluded medications, or it is anticipated that the participant will require treatment with at least 1 of the disallowed concomitant medications during the study evaluation period.
2. Has a hypersensitivity to any proton pump inhibitor (PPI) (including, but not limited to, lansoprazole, omeprazole, rabeprazole, pantoprazole, esomeprazole or ilaprazole), any component of dexlansoprazole, or antacid (example, magnesium trisilicate or similar antacid).
3. Had a history of cancer, (except basal cell carcinoma of the skin), that has not been in remission for at least 5 years prior to Screening.
4. Has a known history or any suspicious Barrett's esophagus with dysplastic changes seen during screening endoscopy.
5. Developed acute upper gastrointestinal bleeding, gastric ulcer (a mucosal defect with white coating) or duodenal ulcer (a mucosal defect with white coating), within 30 days before the start of the Screening Visit (with the possible inclusion of those with gastric or duodenal erosion). The participant requires chronic use (>12 doses per month) of non steroidal anti-inflammatory drugs (NSAIDs) including cyclooxygenase-2 (COX-2) NSAIDs within 30 days prior to the Screening Period and throughout the study.
6. Has comorbidities that could affect the esophagus (eosinophilic esophagitis, esophageal varices, scleroderma, viral or fungal infection, esophageal strictures); a history of radiotherapy or cryotherapy of the esophagus; and a history of corrosive or physiochemical injury (with the possible inclusion in the study of those with Schatzki's ring).
7. Has a history of surgical procedures that may affect the esophagus (example, fundoplication and mechanical dilatation for esophageal strictures) or a history of gastric or duodenal surgery other than endoscopic removal of benign polyps.
8. Participant is known to have the acquired immunodeficiency syndrome (AIDS) or hepatitis, including hepatitis virus carriers (that is, hepatitis B surface antigen HBs-antigen (HBsAg) positive or hepatitis C virus (HCV)-antibody positive).
9. Has current Zollinger-Ellison syndrome (gastric acid hyper secretion) or a history of gastric acid hypersecretion.
10. Participant is scheduled for surgery that requires hospitalization or requires surgical treatment during his/her participation in the study.
11. Has donated or lost >300 milliliter (mL) blood volume, undergone plasmapheresis, or has had a transfusion of any blood product within 90 days prior to the first dose of study drug.
12. Has a history of alcohol or drug abuse (defined as any illicit drug use), or drug addiction in the 12 months prior to Screening.
13. The participant with positive serology result of Helicobacter pylori (H. pylori) that needs eradication therapy during the study participation period as anticipated by the investigator.

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: Healing Period: Dexlansoprazole 60 mg; Dexlansoprazole 60 milligram (mg), delayed-release capsules, orally, once daily for up to 8 weeks in the Healing Period.	Drug: Dexlansoprazole; Dexlansoprazole delayed-release capsules.
Experimental: Healing Period: Lansoprazole 30 mg; Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks in the Healing Period.	Drug: Lansoprazole; Lansoprazole capsules.
Experimental: Maintenance Period: Dexlansprazole 30 mg; Participants who will be healed at Week 8 will be randomized to receive dexlansoprazole 30 mg, delayed-release capsules, orally, once daily for up to 6 months in the Maintenance period.	Drug: Dexlansoprazole; Dexlansoprazole delayed-release capsules.
Experimental: Maintenance Period: Placebo; Participants who will be healed at Week 8 will be randomized to receive dexlansoprazole placebo-matching capsules, orally, once daily for up to 6 months in the Maintenance period.	Drug: Placebo; Dexlansoprazole placebo-matching capsules.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Healing Period: Percentage of Participants With Complete Healing of EE at Week 8	Percentage of participants with complete healing of EE was assessed by endoscopy. EE was graded according to the Los Angeles (LA) classification of esophagitis grading system, based on the extent of visible mucosal breaks seen in the esophagus according to the following: Grade O (no mucosal breaks); Grade A (>=1 mucosal break no longer than 5 millimeter [mm] that does not extend between the tops of 2 mucosal folds); Grade B (>=1 mucosal break greater than [>] 5 mm that does not extend between the tops of 2 mucosal folds); Grade C (>=1 mucosal break that is continuous between the tops of 2 or more mucosal folds, but involves <75 percent (%) of the circumference); Grade D (>=1 mucosal break which involves >=75% of the circumference). Healing is defined as LA Grade O.	Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maintenance Period: Percentage of Participants Who Maintained Complete Healing of EE at Month 6	Percentage of participants with complete healing of EE was assessed by endoscopy. EE was graded according to the LA classification of esophagitis grading system, based on the extent of visible mucosal breaks seen in the esophagus according to the following: Grade O (no mucosal breaks); Grade A (>=1 mucosal break no longer than 5 mm that does not extend between the tops of 2 mucosal folds); Grade B (>=1 mucosal break >5 mm that does not extend between the tops of 2 mucosal folds); Grade C (>=1 mucosal break that is continuous between the tops of 2 or more mucosal folds, but involves <75% of the circumference); Grade D (>=1 mucosal break which involves >=75% of the circumference). Healing is defined as LA Grade O.	Month 6

Collaborators and Investigators

• Sponsor: Takeda

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2016
• Primary Completion (Actual): October 16, 2017
• Study Completion (Actual): November 6, 2017

Study Registration Dates

• First Submitted: August 17, 2016
• First Submitted That Met QC Criteria: August 17, 2016
• First Posted (Estimate): August 19, 2016

Study Record Updates

• Last Update Posted (Actual): February 22, 2019
• Last Update Submitted That Met QC Criteria: October 11, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Drug therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Esophageal Diseases; Esophagitis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Dexlansoprazole; Lansoprazole
• Other Study ID Numbers: TAK-390MR_301; U1111-1142-0320 (Registry Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

Drug and device information, study documents

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