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

Gastroesophageal Reflux Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00255190
• Other study ID #: T-GI04-088
• Secondary ID: U1111-1113-9537
• Status: Completed
• Phase: Phase 3
• First received: November 15, 2005
• Last updated: April 25, 2011
• Start date: January 2006
• Est. completion date: June 2008

Study information

• Verified date: April 2011
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 591
• Est. completion date: June 2008
• Est. primary completion date: June 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Gastroesophageal Reflux
• Gastroesophageal Reflux Disease

Intervention

Drug:
• Dexlansoprazole MR
Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 12 months.
• Dexlansoprazole MR
Dexlansoprazole MR 90 mg, capsules, orally, once daily for up to 12 months.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

United States, 

References & Publications (3)

Dabholkar AH, Han C, Paris MM, Perez MC, Atkinson SN, Peura DA. The 12-month safety profile of dexlansoprazole, a proton pump inhibitor with a dual delayed release formulation, in patients with gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 20 — View Citation

Friedlander EA, Pallentino J, Miller SK, VanBeuge SS. The evolution of proton pump inhibitors for the treatment of gastroesophageal reflux disease. J Am Acad Nurse Pract. 2010 Dec;22(12):674-83. doi: 10.1111/j.1745-7599.2010.00578.x. Epub 2010 Nov 24. Rev — View Citation

Peura DA, Metz DC, Dabholkar AH, Paris MM, Yu P, Atkinson SN. Safety profile of dexlansoprazole MR, a proton pump inhibitor with a novel dual delayed release formulation: global clinical trial experience. Aliment Pharmacol Ther. 2009 Nov 15;30(10):1010-21 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change From Baseline to Month 12 for Hemoglobin Values		Baseline and Month 12	Yes
Primary	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	Yes
Primary	Mean Change From Baseline to Month 12 for Red Blood Cell Count Values		Baseline and Month 12	Yes
Primary	Mean Change From Baseline to Month 12 for Mean Corpuscular Hemoglobin Concentration Values		Baseline and Month 12	Yes
Primary	Mean Change From Baseline to Month 12 for Platelet Count Values		Baseline and Month 12	Yes
Primary	Mean Change From Baseline to Month 12 for White Blood Cell Count Values		Baseline and Month 12	Yes
Primary	Mean Change From Baseline to Month 12 for Blood Urea Nitrogen Values		Baseline and Month 12	Yes
Primary	Mean Change From Baseline to Month 12 for Creatinine Values		Baseline and Month 12	Yes
Primary	Mean Change From Baseline to Month 12 for Calcium Values		Baseline and Month 12	Yes
Primary	Mean Change From Baseline to Month 12 for Inorganic Phosphorus Values		Baseline and Month 12	Yes
Primary	Mean Change From Baseline to Month 12 for Total Bilirubin Values		Baseline and Month 12	Yes
Primary	Mean Change From Baseline to Month 12 for Alkaline Phosphatase Values		Baseline and Month 12	Yes
Primary	Mean Change From Baseline to Month 12 for Aspartate Aminotransferase Values		Baseline and Month 12	Yes
Primary	Mean Change From Baseline to Month 12 for Alanine Aminotransferase Values		Baseline and Month 12	Yes
Primary	Mean Change From Baseline to Month 12 for Serum Gastrin Levels		Baseline and Month 12	Yes
Primary	Mean Change From Baseline to Month 12 for Systolic Blood Pressure		Baseline and Month 12	Yes
Primary	Mean Change From Baseline to Month 12 for Diastolic Blood Pressure		Baseline and Month 12	Yes
Primary	Mean Change From Baseline to Month 12 for Pulse Rate		Baseline and Month 12	Yes
Primary	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)	Yes
Primary	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)	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No

External Links

•   Dexilant Package Insert
•   FDA Safety Alerts and Recalls