Safety and Quality of Life Study of Dexlansoprazole Modified Release Formulation to Treat Heartburn

Study Overview
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Brief Summary
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The purpose of this study is to determine the long-term safety profile of daily treatment with dexlansoprazole MR in subjects with gastroesophageal reflux disease.

Detailed Description
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This open-label study is intended to determine the long-term safety profile of dexlansoprazole MR over 12 months of dosing with 60 mg once-daily (QD) or 90 mg QD in subjects with gastroesophageal reflux disease (GERD), including those with esophageal erosions. Prior to a protocol amendment, 300 subjects successfully completed one of the symptomatic nonerosive gastroesophageal reflux studies T-GD04-082 (NCT00251745) or T-GD04-083 (NCT00251758) in which they were randomly assigned to receive placebo or dexlansoprazole MR 60 or 90 mg QD. Subjects who were enrolled from one of these symptomatic GERD studies were randomly assigned in a 1:1 ratio to receive either dexlansoprazole MR 60 or 90 mg QD in this long-term study. After implementation of protocol amendment #4, an additional 300 subjects with gastroesophageal reflux disease including those with erosive esophagitis will be enrolled and treated with dexlansoprazole MR 90 mg QD for 12 months. Approximately 200 study sites in the U.S. will participate. For all analyses involving visits during treatment from subjects enrolled prior to protocol amendment #4, baseline refers to pretreatment to Study T-GD04-082 (NCT00251745) or T-GD04-083 (NCT00251758). For subjects enrolled under protocol amendment #4, baseline is based on screening or predosing measurement.

Official Title
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A Phase 3, Open-Label Study to Assess the Long-Term Safety of Dexlansoprazole MR (60 mg QD and 90 mg QD)

Conditions
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Gastroesophageal Reflux Disease

Intervention / Treatment
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* Drug: Dexlansoprazole MR
* Drug: Dexlansoprazole MR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have successfully completed either T-GD04-082 (NCT00251745) or T-GD04-083 (NCT00251758) or have a diagnosis of gastroesophageal reflux disease with or without erosive esophagitis. Exclusion Criteria: Any condition that may require inpatient surgery during the course of the study. Use of prescription or non-prescription proton pump inhibitors, histamine (H2) receptor antagonists, sucralfate, misoprostol or prokinetics throughout the study. Use of antacids [except for study supplied Gelusil®]. Subjects using drugs with significant anticholinergic effects such as tricyclics who cannot stay on a stable dose for 4 weeks prior to dosing and throughout the study. Evidence of uncontrolled systemic disease. Allergy to any proton pump inhibitor including Prilosec, Nexium, Prevacid, or others, any component of dexlansoprazole MR, or Gelusil/antacid. Need to take blood thinners. Need to take more than 12 doses of non-steroidal anti-inflammatory drugs per month. Had cancer (except basal cell cancer of the skin) within 3 years prior to screening. Has other esophageal disease including Barrett's esophagus or strictures requiring dilation. Has had radiation or cryotherapy to the esophagus. Has active gastric or duodenal ulcers within 4 weeks of starting study drug. Has a history of hypersecretory conditions such as Zollinger Ellison Syndrome. History of alcohol abuse. Has acquired immunodeficiency syndrome. Has had acute upper gastrointestinal bleeding within 4 weeks of endoscopy. Received a blood product transfusion within 3 months of taking the first dose of study drug. Has previously participated in another dexlansoprazole MR long-term treatment clinical trial.

Ages Eligible for Study
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Minimum Age: 18 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dexlansoprazole MR 60 mg QD<br> | Drug: Dexlansoprazole MR<br>* Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 12 months.<br>* Other names: Dexilant;|
| Experimental: Dexlansoprazole MR 90 mg QD<br> | Drug: Dexlansoprazole MR<br>* Dexlansoprazole MR 90 mg, capsules, orally, once daily for up to 12 months.<br>* Other names: Dexilant;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline to Month 12 for Hemoglobin Values |  | Baseline and Month 12 | 
| Mean Change From Baseline to Month 12 for Hematocrit Values | Hematocrit measurement percent is the absolute difference in Hematocrit values, and not percentage difference. | Baseline and Month 12 | 
| Mean Change From Baseline to Month 12 for Red Blood Cell Count Values |  | Baseline and Month 12 | 
| Mean Change From Baseline to Month 12 for Mean Corpuscular Hemoglobin Concentration Values |  | Baseline and Month 12 | 
| Mean Change From Baseline to Month 12 for Platelet Count Values |  | Baseline and Month 12 | 
| Mean Change From Baseline to Month 12 for White Blood Cell Count Values |  | Baseline and Month 12 | 
| Mean Change From Baseline to Month 12 for Blood Urea Nitrogen Values |  | Baseline and Month 12 | 
| Mean Change From Baseline to Month 12 for Creatinine Values |  | Baseline and Month 12 | 
| Mean Change From Baseline to Month 12 for Calcium Values |  | Baseline and Month 12 | 
| Mean Change From Baseline to Month 12 for Inorganic Phosphorus Values |  | Baseline and Month 12 | 
| Mean Change From Baseline to Month 12 for Total Bilirubin Values |  | Baseline and Month 12 | 
| Mean Change From Baseline to Month 12 for Alkaline Phosphatase Values |  | Baseline and Month 12 | 
| Mean Change From Baseline to Month 12 for Aspartate Aminotransferase Values |  | Baseline and Month 12 | 
| Mean Change From Baseline to Month 12 for Alanine Aminotransferase Values |  | Baseline and Month 12 | 
| Mean Change From Baseline to Month 12 for Serum Gastrin Levels |  | Baseline and Month 12 | 
| Mean Change From Baseline to Month 12 for Systolic Blood Pressure |  | Baseline and Month 12 | 
| Mean Change From Baseline to Month 12 for Diastolic Blood Pressure |  | Baseline and Month 12 | 
| Mean Change From Baseline to Month 12 for Pulse Rate |  | Baseline and Month 12 | 
| Changes From Baseline to Final Visit in Antrum Biopsy Results | Normal=normal tissue; Unknown Baseline = Baseline biopsy not available; Abnormal diagnoses include: Reactive Gastropathy, Chronic Gastritis, Intestinal Metaplasia, Reflective Observation Mucosa-Associated Lymphoid Tissue Lymphoma, Other Abnormal. | Baseline and Final Visit (up to 12 months) | 
| Changes From Baseline to Final Visit in Fundus Biopsy Results | Normal=normal tissue; Unknown Baseline = Baseline biopsy not available; Abnormal diagnoses include: Reactive Gastropathy, Chronic Gastritis, Intestinal Metaplasia, Reflective Observation Mucosa-Associated Lymphoid Tissue Lymphoma, Other Abnormal. | Baseline and Final Visit (up to 12 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline to Month 1 for PAGI-QOL Total Score | Mean overall composite Quality of Life (QOL) score changes were computed in response to 30 questions, each scored 0 (lowest QOL) to 5 (highest QOL). Positive changes from baseline indicate improved QOL. | Baseline and Month 1 | 
| Mean Change From Baseline to Month 3 for PAGI-QOL Total Score | Mean overall composite QOL score changes were computed in response to 30 questions, each scored 0 (lowest QOL) to 5 (highest QOL). Positive changes from baseline indicate improved QOL. | Baseline and Month 3 | 
| Mean Change From Baseline to Month 6 for PAGI-QOL Total Score | Mean overall composite QOL score changes were computed in response to 30 questions, each scored 0 (lowest QOL) to 5 (highest QOL). Positive changes from baseline indicate improved QOL. | Baseline and Month 6 | 
| Mean Change From Baseline to Month 9 for PAGI-QOL Total Score | Mean overall composite QOL score changes were computed in response to 30 questions, each scored 0 (lowest QOL) to 5 (highest QOL). Positive changes from baseline indicate improved QOL. | Baseline and Month 9 | 
| Mean Change From Baseline to Month 12 for PAGI-QOL Total Score | Mean overall composite QOL score changes were computed in response to 30 questions, each scored 0 (lowest QOL) to 5 (highest QOL). Positive changes from baseline indicate improved QOL. | Baseline and Month 12 | 
| Mean Change From Baseline to Month 1 for PAGI-SYM Total Score | Mean overall composite symptom-severity score changes were computed in response to 20 questions, each scored 0 (no symptoms) to 5 (most severe symptoms). Negative changes from baseline indicate improvement in symptoms (decrease in severity). | Baseline and Month 1 | 
| Mean Change From Baseline to Month 3 for PAGI-SYM Total Score | Mean overall composite symptom-severity score changes were computed in response to 20 questions, each scored 0 (no symptoms) to 5 (most severe symptoms). Negative changes from baseline indicate improvement in symptoms (decrease in severity). | Baseline and Month 3 | 
| Mean Change From Baseline to Month 6 for PAGI-SYM Total Score | Mean overall composite symptom-severity score changes were computed in response to 20 questions, each scored 0 (no symptoms) to 5 (most severe symptoms). Negative changes from baseline indicate improvement in symptoms (decrease in severity). | Baseline and Month 6 | 
| Mean Change From Baseline to Month 9 for PAGI-SYM Total Score | Mean overall composite symptom-severity score changes were computed in response to 20 questions, each scored 0 (no symptoms) to 5 (most severe symptoms). Negative changes from baseline indicate improvement in symptoms (decrease in severity). | Baseline and Month 9 | 
| Mean Change From Baseline to Month 12 for PAGI-SYM Total Score | Mean overall composite symptom-severity score changes were computed in response to 20 questions, each scored 0 (no symptoms) to 5 (most severe symptoms). Negative changes from baseline indicate improvement in symptoms (decrease in severity). | Baseline and Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastroesophageal Reflux Disease