Efficacy of Dexlansoprazole MR on Heartburn Control in Participants Previously Receiving Twice Daily Proton Pump Inhibitor Therapy

Phase 3

Completed

• Conditions: Gastroesophageal Reflux
• Interventions: Drug: Dexlansoprazole MR QD

• Registration Number: NCT00847808
• Lead Sponsor: Takeda

Brief Summary

The purpose of this study is to determine if patients with well-controlled heartburn symptoms on twice-daily proton pump inhibitor therapy remain well-controlled after stepping down to once-daily (QD) dexlansoprazole modified release (MR) 30 mg.

Detailed Description

Gastroesophageal reflux disease is recognized as a common and persistent medical problem in the US adult population. Gastroesophageal reflux disease comprises a spectrum of acid-related disorders including symptomatic nonerosive gastroesophageal reflux disease and erosive esophagitis. It affects men and women in nearly equal proportions, and the severity and intensity of heartburn symptoms may be similar in both types of patients.

Dexlansoprazole modified release is a dual delayed release formulation that consists of two types of granules contained in a single capsule. This dual delayed release formulation is designed to extend the duration of drug exposure and maintain pharmacologically active levels over a longer time period.

The purpose of this study is to demonstrate that participants with gastroesophageal reflux disease whose symptoms are well-controlled on twice daily proton pump inhibitors, remain well-controlled when switched to dexlansoprazole MR.

Study Timeline

• Study Start: 2009-02
• Study First Submitted: 2009-02-18
• Study First Submitted QC: 2009-02-18
• Study First Posted: 2009-02-19
• Primary Completion: 2010-04
• Study Completion: 2010-04
• Results First Submitted: 2011-04-05
• Results First Submitted QC: 2011-04-05
• Results First Posted: 2011-04-29
• Status Verified: 2012-02
• Last Update Submitted: 2012-02-01
• Last Update Posted: 2012-02-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 178

Inclusion Criteria

1. Prior to any study-specific procedures being performed, the participant voluntarily signs an Investigational Review Board-approved informed consent form (ICF) and any privacy statement/authorization form required (eg, The Health Insurance Portability and Accountability Act (HIPAA) authorization)
2. Has a history of gastroesophageal reflux disease symptom, including heartburn, prior to therapy, who are currently being treated with twice daily proton pump inhibitors, excluding Dexilant (dexlansoprazole).
3. Taking a stable dose of any twice daily proton pump inhibitors for less than or equal to 1 year and greater than 8 weeks prior to Screening.
4. Participant is well-controlled on their current twice daily proton pump inhibitors.
5. Females cannot be nursing and must have a negative urine pregnancy test at Day -1 or be of non-childbearing potential. If females are of child bearing potential, must have a negative serum human chorionic gonadotropin (hCG) pregnancy test during Screening and on an acceptable form of contraception, or have had bilateral tubal ligation if performed a minimum of 90 days prior to Day 1.

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Exclusion Criteria

1. Has a history of co-existing diseases affecting the esophagus, history of radiation therapy or cryotherapy to the esophagus, caustic or physiochemical trauma such as sclerotherapy to the esophagus.

2. Has active gastric or duodenal ulcers during the 30 days prior to Screening.

3. Has acute upper gastrointestinal hemorrhage during the 30 days prior to Screening.

4. Has current or historical evidence of Zollinger-Ellison syndrome or other hypersecretory condition.

5. Has known hypersensitivity to any proton pump inhibitor or any component of dexlansoprazole MR.

6. Use of any Histamine type-2 receptor antagonist or antacids during Screening or anticipated use during the study treatment period.

7. Use of the following medications 7 days prior to Screening or anticipated use during the study:

   • Sucralfate.
   • Misoprostol.
   • Systemic corticosteroids.
   • Prokinetics (to include metoclopramide, cisapride, tegaserod).
   • Bisphosphonates during the 6 months prior to Screening or anticipated use during the study.
   • Chronic use (> 12 doses per month) of nonsteroidal anti-inflammatory drugs
   • Drugs with significant anticholinergic effects such as tricyclic antidepressants or drugs with central nervous system effects that could mask perception of symptoms.
   • Any investigational drug(s) within 30 days of Screening.

8. Has received blood products within the 3 months prior to Screening.

9. History of alcohol abuse or illegal drug use or drug addiction in the 12 months prior to Screening.

10. Evidence of uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, or endocrine disease or other abnormality, which may impact the ability of the participant to participate or potentially confound the study results.

11. Atypical manifestations of gastroesophageal reflux disease.

12. Has abnormal screening laboratory values that suggest a clinically significant underlying disease or condition.

13. Cancer within 5 years prior to Screening.

14. Is known to have acquired immunodeficiency syndrome.

15. Has any condition that is likely to require inpatient surgery during the course of the study.

16. Surgery of the acute upper gastrointestinal tract, including bariatric.

17. Is in the opinion of the investigator unable to comply with the requirements of the study or are unsuitable for any reason.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	Dexlansoprazole MR QD	-

Primary Outcome Measures

Name	Time	Method
Proportion of Participants Who Remain Well Controlled After Switching From Their Current Twice-daily Proton Pump Inhibitor Therapy to Dexlansoprazole MR.	Week 3 through Week 6	Well-controlled participants were defined to be participants who completed the study having at least 23 days of evaluable diary entries between Days 15 and 42, inclusive, and had ≤4 occurrences of heartburn during this period.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in the Patient Assessment of Upper Gastrointestinal Disorders - Quality of Life (PAGI-QOL) - Daily Activities Subscale in Participants Who Remain Well-controlled.	Baseline and Week 6.	PAGI-QOL is a 30-item self-reported instrument assessing health-related quality of life impact of upper gastrointestinal disorders. It includes 30 items across five subscales (daily activities, clothing, diet/food habits, relationship, psychological well-being and distress), scored on a 6-point Likert scale with subscale and total score ranging from 0 (none) to 5 (all the time). For reporting purposes, the scores are reversed and higher scores reflect improved quality of life and positive changes from baseline indicate improved quality of life.
Change From Baseline in the Patient Assessment of Upper Gastrointestinal Disorders - Quality of Life (PAGI-QOL) - Clothing Subscale in Participants Who Remain Well-controlled.	Baseline and Week 6.	PAGI-QOL is a 30-item self-reported instrument assessing health-related quality of life impact of upper gastrointestinal disorders. It includes 30 items across five subscales (daily activities, clothing, diet/food habits, relationship, psychological well-being and distress), scored on a 6-point Likert scale with subscale and total score ranging from 0 (none) to 5 (all the time). For reporting purposes, the scores are reversed and higher scores reflect improved quality of life and positive changes from baseline indicate improved quality of life.
Change From Baseline in the Patient Assessment of Upper Gastrointestinal Disorders - Quality of Life (PAGI-QOL) - Diet and Food Habits Subscale in Participants Who Remain Well-controlled.	Baseline and Week 6.	PAGI-QOL is a 30-item self-reported instrument assessing health-related quality of life impact of upper gastrointestinal disorders. It includes 30 items across five subscales (daily activities, clothing, diet/food habits, relationship, psychological well-being and distress), scored on a 6-point Likert scale with subscale and total score ranging from 0 (none) to 5 (all the time). For reporting purposes, the scores are reversed and higher scores reflect improved quality of life and positive changes from baseline indicate improved quality of life.
Change From Baseline in the Patient Assessment of Upper Gastrointestinal Disorders - Quality of Life (PAGI-QOL) - Relationship Subscale in Participants Who Remain Well-controlled.	Baseline and Week 6.	PAGI-QOL is a 30-item self-reported instrument assessing health-related quality of life impact of upper gastrointestinal disorders. It includes 30 items across five subscales (daily activities, clothing, diet/food habits, relationship, psychological well-being and distress), scored on a 6-point Likert scale with subscale and total score ranging from 0 (none) to 5 (all the time). For reporting purposes, the scores are reversed and higher scores reflect improved quality of life and positive changes from baseline indicate improved quality of life.
Change From Baseline in the Patient Assessment of Upper Gastrointestinal Disorders - Quality of Life (PAGI-QOL) - Psychological Well-being Subscale in Participants Who Remain Well-controlled.	Baseline and Week 6.	PAGI-QOL is a 30-item self-reported instrument assessing health-related quality of life impact of upper gastrointestinal disorders. It includes 30 items across five subscales (daily activities, clothing, diet/food habits, relationship, psychological well-being and distress), scored on a 6-point Likert scale with subscale and total score ranging from 0 (none) to 5 (all the time). For reporting purposes, the scores are reversed and higher scores reflect improved quality of life and positive changes from baseline indicate improved quality of life.
Change From Baseline in the Patient Assessment of Upper Gastrointestinal Disorders - Quality of Life (PAGI-QOL) - Total Score in Participants Who Remain Well-controlled.	Baseline and Week 6.	PAGI-QOL is a 30-item self-reported instrument assessing health-related quality of life impact of upper gastrointestinal disorders. It includes 30 items across five subscales (daily activities, clothing, diet/food habits, relationship, psychological well-being and distress), scored on a 6-point Likert scale with subscale and total score ranging from 0 (none) to 5 (all the time). For reporting purposes, the scores are reversed and higher scores reflect improved quality of life and positive changes from baseline indicate improved quality of life.
Change From Baseline in Patient Assessment of Upper Gastrointestinal Disorders - Symptom Severity Index (PAGI-SYM) - Nausea/Vomiting Subscale in Participants Who Remain Well-controlled.	Baseline and Week 6.	PAGI-SYM is a 20-item self-reported questionnaire that measures symptom severity of upper gastrointestinal disorders across six subscales (nausea/vomiting, fullness/early satiety, bloating, upper abdominal pain, lower abdominal pain, heartburn/regurgitation) which are summarized by individual subscale scores and a total score. The items are rated on a 6-point Likert scale with subscale and total score ranging from 0 (none) to 5 (very severe). Higher scores indicate higher symptom severity and thus negative changes from baseline indicate decrease in symptom severity.
Change From Baseline in Patient Assessment of Upper Gastrointestinal Disorders - Symptom Severity Index (PAGI-SYM) - Fullness/Early Satiety Subscale in Participants Who Remain Well-controlled.	Baseline and Week 6.	PAGI-SYM is a 20-item self-reported questionnaire that measures symptom severity of upper gastrointestinal disorders across six subscales (nausea/vomiting, fullness/early satiety, bloating, upper abdominal pain, lower abdominal pain, heartburn/regurgitation) which are summarized by individual subscale scores and a total score. The items are rated on a 6-point Likert scale with subscale and total score ranging from 0 (none) to 5 (very severe). Higher scores indicate higher symptom severity and thus negative changes from baseline indicate decrease in symptom severity.
Change From Baseline in Patient Assessment of Upper Gastrointestinal Disorders - Symptom Severity Index (PAGI-SYM) - Bloating Subscale in Participants Who Remain Well-controlled.	Baseline and Week 6.	PAGI-SYM is a 20-item self-reported questionnaire that measures symptom severity of upper gastrointestinal disorders across six subscales (nausea/vomiting, fullness/early satiety, bloating, upper abdominal pain, lower abdominal pain, heartburn/regurgitation) which are summarized by individual subscale scores and a total score. The items are rated on a 6-point Likert scale with subscale and total score ranging from 0 (none) to 5 (very severe). Higher scores indicate higher symptom severity and thus negative changes from baseline indicate decrease in symptom severity.
Change From Baseline in Patient Assessment of Upper Gastrointestinal Disorders - Symptom Severity Index (PAGI-SYM) - Upper Abdominal Pain Subscale in Participants Who Remain Well-controlled.	Baseline and Week 6.	PAGI-SYM is a 20-item self-reported questionnaire that measures symptom severity of upper gastrointestinal disorders across six subscales (nausea/vomiting, fullness/early satiety, bloating, upper abdominal pain, lower abdominal pain, heartburn/regurgitation) which are summarized by individual subscale scores and a total score. The items are rated on a 6-point Likert scale with subscale and total score ranging from 0 (none) to 5 (very severe). Higher scores indicate higher symptom severity and thus negative changes from baseline indicate decrease in symptom severity.
Change From Baseline in Patient Assessment of Upper Gastrointestinal Disorders - Symptom Severity Index (PAGI-SYM) - Lower Abdominal Pain Subscale in Participants Who Remain Well-controlled.	Baseline and Week 6.	PAGI-SYM is a 20-item self-reported questionnaire that measures symptom severity of upper gastrointestinal disorders across six subscales (nausea/vomiting, fullness/early satiety, bloating, upper abdominal pain, lower abdominal pain, heartburn/regurgitation) which are summarized by individual subscale scores and a total score. The items are rated on a 6-point Likert scale with subscale and total score ranging from 0 (none) to 5 (very severe). Higher scores indicate higher symptom severity and thus negative changes from baseline indicate decrease in symptom severity.
Change From Baseline in Patient Assessment of Upper Gastrointestinal Disorders - Symptom Severity Index (PAGI-SYM) - Heartburn/Regurgitation Subscale in Participants Who Remain Well-controlled.	Baseline and Week 6.	PAGI-SYM is a 20-item self-reported questionnaire that measures symptom severity of upper gastrointestinal disorders across six subscales (nausea/vomiting, fullness/early satiety, bloating, upper abdominal pain, lower abdominal pain, heartburn/regurgitation) which are summarized by individual subscale scores and a total score. The items are rated on a 6-point Likert scale with subscale and total score ranging from 0 (none) to 5 (very severe). Higher scores indicate higher symptom severity and thus negative changes from baseline indicate decrease in symptom severity.
Change From Baseline in Patient Assessment of Upper Gastrointestinal Disorders - Symptom Severity Index (PAGI-SYM) - Total Score in Participants Who Remain Well-controlled.	Baseline and Week 6.	PAGI-SYM is a 20-item self-reported questionnaire that measures symptom severity of upper gastrointestinal disorders across six subscales (nausea/vomiting, fullness/early satiety, bloating, upper abdominal pain, lower abdominal pain, heartburn/regurgitation) which are summarized by individual subscale scores and a total score. The items are rated on a 6-point Likert scale with subscale and total score ranging from 0 (none) to 5 (very severe). Higher scores indicate higher symptom severity and thus negative changes from baseline indicate decrease in symptom severity.