A Study of Dexlansoprazole in Healing and Maintenance of Healed Erosive Esophagitis (EE) in Children

Study Overview
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Brief Summary
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The main aims of the study are to check the side effects and effectiveness of Dexlansoprazole in healing erosive esophagitis (EE) side effects and effectiveness of Dexlansoprazole in maintaining healed EE in children. Participants will take Dexlansoprazole by mouth.

Detailed Description
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The drug being tested in this study is called dexlansoprazole. Dexlansoprazole is being tested to heal EE and maintain healing of EE in pediatric participants aged 2 to 11 years. This study will look at the healing of EE followed by maintained healing of EE in children who take dexlansoprazole. The study will be conducted in two periods; a Healing of EE Period and a Maintenance of Healed EE Period. Approximately 76 patients will be enrolled in this study. Participants will be randomly assigned (by chance, like flipping a coin) to receive dexlansoprazole 60 mg or dexlansoprazole 30 mg for 8 weeks during the Healing of EE Period. Following Week 8, participants will enter the Maintenance of Healed EE Period and will receive half their healing dose of dexlansoprazole, (i.e., either 30 mg, dexlansoprazole 15 mg). All participants will be asked to take one capsule at the same time each day throughout the study. All participants will be asked to record any time they have heartburn symptoms in a diary. Participants who complete the 16 weeks of the Maintenance of Healed EE Period (Week 24) and have maintained healing of EE as confirmed by endoscopy, will enter a Post-Treatment Follow up Period for up to 3 months after the last dose of study drug. During this period participants will continue to complete the symptom questionnaires daily in the eDiaries and return for a clinic visit each month. Participants who require an invasive procedure or treatment with a proton pump inhibitor (PPI) or histamine 2-receptor antagonist (H2RA) for gastroesophageal reflux disease (GERD)/EE will be discontinued from the Post-Treatment Follow-up Period and a Final Study Visit will be performed. This multi-center trial will be conducted worldwide. The overall time to participate in this study is up to 10 months. Participants will make multiple visits to the clinic including a final visit 3 months after last dose of study drug for a follow-up assessment.

Official Title
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A Phase 2, Double-Blind, 36-Week, Multicenter Study to Assess the Safety and Effectiveness of Daily Oral Administration of Dexlansoprazole Delayed-Release Capsules for Healing of Erosive Esophagitis (EE) and Maintenance of Healed EE in Pediatric Subjects Aged 2 to 11 Years With EE

Conditions
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Erosive Esophagitis

Intervention / Treatment
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* Drug: Dexlansoprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In the opinion of the investigator, the participant (as age appropriate) and/or parent(s) or legal guardian are capable of understanding and complying with protocol requirements. Prior to any study-specific procedures being performed, the appropriate screening informed consent and the assent forms (as applicable) must be signed and dated by parent(s) or legal guardian and by the participant respectively, if appropriate. Has a medical history of symptoms of GERD for at least 3 months prior to Screening. Has medical history of at least 1 failed attempted withdrawal of prior PPI/acid-suppressive therapy with a return of symptoms upon withdrawal. Has met the eDiary qualification criteria as assessed by the PGSDD, defined as hurting or burning in the stomach, chest, or throat on at least 3 of any 7 consecutive days during the Screening Period. (Note: If an endoscopy performed within 1 week of signing screening informed consent and assent [as applicable] is used to confirm diagnosis of EE, the participant does not need to meet this criterion). Has endoscopic evidence of EE with LA Grade A to D based on the screening endoscopy performed either during the Screening Period or within 1 week prior to signing screening informed consent and assent (as applicable). An endoscopy that was performed within 1 week prior to signing screening informed consent and assent, as applicable, is an acceptable replacement for the Screening endoscopy if EE is documented by LA classification scale criterion previously described, protocol-required biopsies were collected and endoscopic pictures were obtained. Is male or female and age 2 to 11 years, inclusive, at the time of screening informed consent. Exclusion Criteria: Has evidence of cardiovascular, pulmonary, central nervous system, hepatic, hematopoietic, renal, or metabolic disorder, severe allergy, asthma, or allergic skin rash that suggests any uncontrolled, clinically significant underlying disease or condition (other than the disease being studied), which may impact the ability of the participant to participate or potentially confound the study results. Has a coexisting disease affecting the esophagus (eg, esophageal varices, scleroderma, viral or fungal infection, or esophageal stricture), history of radiation therapy or cryotherapy to the esophagus, caustic or physiochemical trauma such as sclerotherapy to the esophagus. Has any findings in his/her medical history, physical examination, or safety clinical laboratory tests giving reasonable suspicion of underlying disease that might interfere with the conduct of the trial. Has a history of hypersensitivity or allergies to dexlansoprazole or any component of dexlansoprazole capsules or any PPI (including lansoprazole, omeprazole, rabeprazole, pantoprazole, or esomeprazole) or antacids. 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. Has a condition that may require inpatient surgery during the course of the study. Has a known history of Barrett's with dysplastic changes in the esophagus. Has a known history of eosinophilic esophagitis (EoE) or endoscopic or histologic findings suggestive of EoE (≥15 eosinophils per high-powered field [HPF]). Has history of celiac disease, tests positive for tissue transglutaminase (tTG) antibody, or has confirmed disease by histology. Has history of inflammatory bowel disease, or irritable bowel syndrome. Has active gastric or duodenal ulcers within 4 weeks prior to Day -1. If present >4 weeks prior to Day -1, ulcers must not be present upon screening endoscopy. Requires dilatation of esophageal strictures and/or strictures preventing passage of the endoscope during the Screening endoscopy. Schatzki's ring (a ring of mucosal tissue near the lower esophageal sphincter) is acceptable. A female participant who has reached menarche by Day -1. Is known to be positive for the human immunodeficiency virus (HIV). Has current or clinical history of Zollinger-Ellison syndrome or other hypersecretory condition. Has a history of gastric, duodenal, or esophageal surgery except simple oversew of an ulcer. A history of gastric tube and/or percutaneous endoscopic gastrostomy (PEG) placement is allowed. Had an acute upper gastrointestinal hemorrhage within 4 weeks prior to endoscopy. Has donated or lost >10% of the total blood volume, undergone plasmapheresis, or has had a transfusion of any blood product within 90 days prior to the first dose of study drug. Has a known history of alcohol abuse or illegal drug use within the past 12 months prior to the first dose of study drug. Has any screening abnormal laboratory value that suggests a clinically significant underlying disease or condition that may prevent the participant from entering the study; or the participant has: creatinine >1.5 mg/dL, alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >2 times the upper limit of normal (×ULN), or total bilirubin >2.0 mg/dL with AST/ALT elevated above the limits of normal values. Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in the conduct of this study or may consent and assent under duress. Students of the institution/research facility who are under the supervision of, or in a subordinate role to, the investigator are also ineligible. The participant, in the opinion of the investigator, is unlikely to comply with the protocol or is unsuitable for any other reason. Has participated in another clinical study (not including screening for Study TAK-390MR_204 [NCT02616302]) and/or has received any investigational compound within 30 days prior to Screening. Tests positive for H. pylori.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 11 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healing Period: Dexlansoprazole 60 mg<br>Dexlansoprazole 60 mg, capsules, orally, once, daily, for 8 weeks. | Drug: Dexlansoprazole<br>* Dexlansoprazole capsules<br>* Other names: Dexilant;|
| Experimental: Healing Period: Dexlansoprazole 30 mg<br>Dexlansoprazole 30 mg, capsules, orally, once, daily, for 8 weeks. | Drug: Dexlansoprazole<br>* Dexlansoprazole capsules<br>* Other names: Dexilant;|
| Experimental: Maintenance of Healed EE: Dexlansoprazole 30 mg<br>Participants on Dexlansoprazole 60 mg treatment arm in Healing Period will receive half dose, dexlansoprazole 30 mg, capsules, orally, once, daily, for 16 weeks in the Maintenance Period. | Drug: Dexlansoprazole<br>* Dexlansoprazole capsules<br>* Other names: Dexilant;|
| Experimental: Maintenance of Healed EE: Dexlansoprazole 15 mg<br>Participants on Dexlansoprazole 30 mg treatment arm in Healing Period will receive half dose, dexlansoprazole 15 mg, capsules, orally, once, daily, for 16 weeks in the Maintenance Period. | Drug: Dexlansoprazole<br>* Dexlansoprazole capsules<br>* Other names: Dexilant;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Healing of Erosive Esophagitis (EE) by Week 8 | Healing of EE will be assessed by endoscopy. | Week 8 | 
| Percentage of Participants who Maintained Healed EE from Week 8 to Week 24 | Percentage of participants who maintained healed EE from Week 8 to Week 24 among the participants who were healed at Week 8 as assessed by endoscopy. | Week 8 to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Days Without Hurting or Burning in the Stomach, Chest or Throat Over the First 8 Weeks of Treatment | Daily electronic diaries (eDiaries) will be completed which contain Pediatric Gastroesophageal Reflux Disease Symptom Daily Diaries (PGSDD) questionnaires that document presence or absence of hurting or burning in the stomach, chest or throat vomiting, regurgitation and trouble eating. Parents or caregivers of participants aged 2 to 8 years will complete the PGSDD (parent) in the eDiary for their child and participants aged 9 to 11 years will complete PGSDD (child) in the eDiary themselves. The eDiaries will be completed on a daily basis reflecting a continuous 24-hour period. | Week 8 | 
| Percentage of Days Without Hurting or Burning in the Stomach, Chest or Throat Over Weeks 8 to 24 Among Participants Who were Healed by Week 8 | Daily eDiaries will be completed which contain PGSDD questionnaires that document presence or absence of hurting or burning in the stomach, chest or throat vomiting, regurgitation and trouble eating. Parents or caregivers of participants aged 2 to 8 years will complete the PGSDD (parent) in the eDiary for their child and participants aged 9 to 11 years will complete PGSDD (child) in the eDiary themselves. The eDiaries will be completed on a daily basis reflecting a continuous 24-hour period. | Weeks 8 to 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug therapy