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Comparison of Dexlansoprazole MR to Placebo on the Ability to Maintain Healing in Subjects With Healed Erosive Esophagitis

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ClinicalTrials.gov Identifier: NCT00255151
Recruitment Status : Completed
First Posted : November 17, 2005
Results First Posted : August 28, 2009
Last Update Posted : February 3, 2012
Sponsor:
Information provided by (Responsible Party):
Takeda

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Esophagitis, Reflux
Esophagitis, Peptic
Interventions Drug: Dexlansoprazole MR
Drug: Placebo
Enrollment 451

Recruitment Details Subjects were enrolled at 105 sites in the United States; date of first dose (04 January 2006; date of last procedure: 14 November 2006).
Pre-assignment Details Subjects had to have endoscopically proven healed erosive esophagitis (EE) after 4 to 8 weeks of treatment with lansoprazole 30 mg once-daily (QD), dexlansoprazole modified release (MR) 60 mg QD, or dexlansoprazole MR 90 mg QD in the EE healing studies, T-EE04-084 (NCT00251693) and T-EE04-085 (NCT00251719).
Arm/Group Title Placebo QD Dexlansoprazole MR 60 mg QD Dexlansoprazole MR 90 mg QD
Hide Arm/Group Description Placebo capsules, orally, once daily for up to 6 months. Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 6 months. Dexlansoprazole MR 90 mg, capsules, orally, once daily for up to 6 months.
Period Title: Overall Study
Started 140 159 152
Completed 17 110 103
Not Completed 123 49 49
Reason Not Completed
Adverse Event             10             6             9
Lost to Follow-up             4             3             4
Withdrawal by Subject             18             17             8
Noncompliance             0             1             2
Subject Request/Subject Unavailable             1             1             2
Relapse of Erosive Esophagitis             78             16             12
Possible Barrett's Esophagus             1             3             8
Esophageal Stricture             0             0             1
Therapeutic Failure             11             2             3
Arm/Group Title Placebo QD Dexlansoprazole MR 60 mg QD Dexlansoprazole MR 90 mg QD Total
Hide Arm/Group Description Placebo capsules, orally, once daily for up to 6 months. Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 6 months. Dexlansoprazole MR 90 mg, capsules, orally, once daily for up to 6 months. Total of all reporting groups
Overall Number of Baseline Participants 140 159 152 451
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 140 participants 159 participants 152 participants 451 participants
48.2  (12.88) 49.7  (12.66) 48.8  (13.76) 48.9  (13.09)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 140 participants 159 participants 152 participants 451 participants
<45 years 48 55 56 159
45 to <65 years 81 86 81 248
≥65 years 11 18 15 44
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 140 participants 159 participants 152 participants 451 participants
Female
70
  50.0%
76
  47.8%
70
  46.1%
216
  47.9%
Male
70
  50.0%
83
  52.2%
82
  53.9%
235
  52.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 140 participants 159 participants 152 participants 451 participants
American Indian or Alaska Native
2
   1.4%
2
   1.3%
1
   0.7%
5
   1.1%
Asian
2
   1.4%
3
   1.9%
0
   0.0%
5
   1.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
11
   7.9%
17
  10.7%
11
   7.2%
39
   8.6%
White
124
  88.6%
135
  84.9%
136
  89.5%
395
  87.6%
More than one race
1
   0.7%
2
   1.3%
4
   2.6%
7
   1.6%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 140 participants 159 participants 152 participants 451 participants
Hispanic or Latino
15
  10.7%
19
  11.9%
14
   9.2%
48
  10.6%
Not Hispanic or Latino
125
  89.3%
140
  88.1%
138
  90.8%
403
  89.4%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Baseline Los Angeles (LA) Classification Grade for Erosive Esophagitis (EE)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 140 participants 159 participants 152 participants 451 participants
A: ≥1 mucosal break <5 mm 58 60 54 172
B: ≥1 mucosal break ≥5 mm 48 61 58 167
C: ≥1 mucosal break <75% of circumference 28 33 32 93
D: ≥1 mucosal break ≥75% of circumference 6 5 8 19
[1]
Measure Description: Baseline values from Studies T-EE04-084 (NCT00251693)and T-EE04-085 (NCT00251719), with severity of EE increasing from Grade A to Grade D.
1.Primary Outcome
Title Percentage of Subjects Who Maintained Complete Healing of Erosive Esophagitis as Assessed by Endoscopy - Crude Rate Analysis.
Hide Description Crude rates analyzed maintenance of healed EE from baseline of this study and considered prematurely discontinued subjects as relapsed.
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The crude rate analysis was performed on intent-to-treat (ITT) subjects (subjects from Studies T-EE04-084 or T-EE04-085 with endoscopically proven healed EE who received at least 1 dose of study drug in this study and did not have a gap of >7 days between the EE healing studies and this study) with at least one endoscopy in this maintenance study.
Arm/Group Title Placebo QD Dexlansoprazole MR 60 mg QD Dexlansoprazole MR 90 mg QD
Hide Arm/Group Description:
Placebo capsules, orally, once daily for up to 6 months.
Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 6 months.
Dexlansoprazole MR 90 mg, capsules, orally, once daily for up to 6 months.
Overall Number of Participants Analyzed 112 152 138
Measure Type: Number
Unit of Measure: Percentage of Subjects
14.3 66.4 64.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo QD, Dexlansoprazole MR 60 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments Hochberg’s method was used to ensure that the overall 0.0025 level of significance was maintained for the pairwise comparisons between each dexlansoprazole MR dose and placebo.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo QD, Dexlansoprazole MR 90 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments Hochberg’s method was used to ensure that the overall 0.0025 level of significance was maintained for the pairwise comparisons between each dexlansoprazole MR dose and placebo.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Dexlansoprazole MR 60 mg QD, Dexlansoprazole MR 90 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.80473
Comments Statistical significance was determined at 0.0025 level without adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
2.Primary Outcome
Title Percentage of Subjects Who Maintained Complete Healing of Erosive Esophagitis as Assessed by Endoscopy - Life Table Method
Hide Description Percentage of subjects who maintained complete healing of erosive esophagitis as assessed by endoscopy. In the life table method, subjects without post-baseline endoscopy were included as censored; subjects who did not have a recurrence of EE and did not complete the study were also considered censored.
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Life table method for the maintenance rate of healed EE was performed on ITT subjects and included subjects without post-baseline endoscopy as censored.
Arm/Group Title Placebo QD Dexlansoprazole MR 60 mg QD Dexlansoprazole MR 90 mg QD
Hide Arm/Group Description:
Placebo capsules, orally, once daily for up to 6 months.
Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 6 months.
Dexlansoprazole MR 90 mg, capsules, orally, once daily for up to 6 months.
Overall Number of Participants Analyzed 140 159 152
Measure Type: Number
Unit of Measure: Percentage of Subjects
25.7 86.6 82.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo QD, Dexlansoprazole MR 60 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments Hochberg’s method was used to ensure that the overall 0.0025 level of significance was maintained for the pairwise comparisons between each dexlansoprazole MR dose and placebo.
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo QD, Dexlansoprazole MR 90 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments Hochberg’s method was used to ensure that the overall 0.0025 level of significance was maintained for the pairwise comparisons between each dexlansoprazole MR dose and placebo.
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Dexlansoprazole MR 60 mg QD, Dexlansoprazole MR 90 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.37161
Comments Statistical significance was determined at 0.0025 level without adjustment for multiple comparisons.
Method Log Rank
Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Days Without Daytime or Nighttime Heartburn as Assessed by Daily Diary-Median.
Hide Description The percentage was calculated as the days that were heartburn-free out of the total number of days for which either a daytime or nighttime result was reported.
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis of 24-hour heartburn-free days was performed on ITT subjects with at least one daytime or nighttime heartburn Yes/No question answered during treatment.
Arm/Group Title Placebo QD Dexlansoprazole MR 60 mg QD Dexlansoprazole MR 90 mg QD
Hide Arm/Group Description:
Placebo capsules, orally, once daily for up to 6 months.
Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 6 months.
Dexlansoprazole MR 90 mg, capsules, orally, once daily for up to 6 months.
Overall Number of Participants Analyzed 133 157 147
Median (Inter-Quartile Range)
Unit of Measure: Percentage of Days
19.2
(5.0 to 52.0)
95.8
(76.9 to 99.1)
94.4
(67.1 to 99.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo QD, Dexlansoprazole MR 60 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments The 0.0025 level of significance for this secondary endpoint was controlled using Hochberg's method for comparisons of each dexlansoprazole MR dose to placebo.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo QD, Dexlansoprazole MR 90 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments The 0.0025 level of significance for this secondary endpoint was controlled using Hochberg's method for comparisons of each dexlansoprazole MR dose to placebo.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Dexlansoprazole MR 60 mg QD, Dexlansoprazole MR 90 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.76046
Comments Statistical significance was determined at 0.0025 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Days Without Daytime or Nighttime Heartburn as Assessed by Daily Diary-Mean.
Hide Description The percentage was calculated as the days that were heartburn-free out of the total number of days for which either a daytime or nighttime result was marked
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis of 24-hour heartburn-free days was performed on ITT subjects with at least one daytime or nighttime heartburn Yes/No question answered during treatment.
Arm/Group Title Placebo QD Dexlansoprazole MR 60 mg QD Dexlansoprazole MR 90 mg QD
Hide Arm/Group Description:
Placebo capsules, orally, once daily for up to 6 months.
Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 6 months.
Dexlansoprazole MR 90 mg, capsules, orally, once daily for up to 6 months.
Overall Number of Participants Analyzed 133 157 147
Mean (Standard Deviation)
Unit of Measure: Percentage of Days
29.5  (29.3) 79.7  (30.7) 79.2  (30.0)
5.Secondary Outcome
Title Percentage of Days Without Nighttime Heartburn as Assessed by Daily Diary-Median.
Hide Description The percentage was calculated as the nights that were heartburn-free out of the total number of days for which a nighttime result was marked.
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on ITT subjects with at least one nighttime heartburn Yes/No question answered during treatment.
Arm/Group Title Placebo QD Dexlansoprazole MR 60 mg QD Dexlansoprazole MR 90 mg QD
Hide Arm/Group Description:
Placebo capsules, orally, once daily for up to 6 months.
Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 6 months.
Dexlansoprazole MR 90 mg, capsules, orally, once daily for up to 6 months.
Overall Number of Participants Analyzed 133 157 147
Median (Inter-Quartile Range)
Unit of Measure: Percentage of Days
50.0
(14.8 to 81.3)
98.3
(90.6 to 100.0)
97.1
(83.3 to 100.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo QD, Dexlansoprazole MR 60 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments The 0.0025 level of significance for this secondary endpoint was controlled using Hochberg's method for comparisons of each dexlansoprazole MR dose to placebo.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo QD, Dexlansoprazole MR 90 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments The 0.0025 level of significance for this secondary endpoint was controlled using Hochberg's method for comparisons of each dexlansoprazole MR dose to placebo.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Dexlansoprazole MR 60 mg QD, Dexlansoprazole MR 90 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.59700
Comments Statistical significance was determined at the 0.0025 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Days Without Nighttime Heartburn as Assessed by Daily Diary-Mean.
Hide Description The percentage was calculated as the nights that were heartburn-free out of the total number of days for which a nighttime result was marked.
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on ITT subjects with at least one nighttime heartburn Yes/No question answered during treatment.
Arm/Group Title Placebo QD Dexlansoprazole MR 60 mg QD Dexlansoprazole MR 90 mg QD
Hide Arm/Group Description:
Placebo capsules, orally, once daily for up to 6 months.
Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 6 months.
Dexlansoprazole MR 90 mg, capsules, orally, once daily for up to 6 months.
Overall Number of Participants Analyzed 133 157 147
Mean (Standard Deviation)
Unit of Measure: Percentage of Days
48.3  (35.3) 87.1  (25.5) 85.4  (26.3)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo QD Dexlansoprazole MR 60 mg QD Dexlansoprazole MR 90 mg QD
Hide Arm/Group Description Placebo capsules, orally, once daily for up to 6 months. Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 6 months. Dexlansoprazole MR 90 mg, capsules, orally, once daily for up to 6 months.
All-Cause Mortality
Placebo QD Dexlansoprazole MR 60 mg QD Dexlansoprazole MR 90 mg QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo QD Dexlansoprazole MR 60 mg QD Dexlansoprazole MR 90 mg QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0   2   5 
Cardiac disorders       
Coronary Artery Disorders Not Elsewhere Classified (NEC)  1  0/140 (0.00%)  0/159 (0.00%)  1/152 (0.66%) 
Gastrointestinal disorders       
Acute and Chronic Pancreatitis  1  0/140 (0.00%)  0/159 (0.00%)  1/152 (0.66%) 
General disorders       
Pain and Discomfort NEC  1  0/140 (0.00%)  1/159 (0.63%)  0/152 (0.00%) 
Injury, poisoning and procedural complications       
Non-site Specific Injuries NEC  1  0/140 (0.00%)  0/159 (0.00%)  1/152 (0.66%) 
Musculoskeletal and connective tissue disorders       
Musculoskeletal and Connective Tissue Signs and Symptoms NEC  1  0/140 (0.00%)  0/159 (0.00%)  1/152 (0.66%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Breast and Nipple Neoplasms Malignant  1  0/140 (0.00%)  0/159 (0.00%)  1/152 (0.66%) 
Reproductive system and breast disorders       
Uterine Disorders NEC  1  0/140 (0.00%)  1/159 (0.63%)  0/152 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 9.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo QD Dexlansoprazole MR 60 mg QD Dexlansoprazole MR 90 mg QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   7   33   25 
Gastrointestinal disorders       
Diarrhoea (Excluding [Excl] Infective)  1  1/140 (0.71%)  10/159 (6.29%)  10/152 (6.58%) 
Flatulence, Bloating and Distension  1  0/140 (0.00%)  8/159 (5.03%)  3/152 (1.97%) 
Gastritis (Excl Infective)  1  1/140 (0.71%)  10/159 (6.29%)  6/152 (3.95%) 
Gastrointestinal and Abdominal Pains (Excl Oral and Throat)  1  2/140 (1.43%)  10/159 (6.29%)  6/152 (3.95%) 
Infections and infestations       
Upper Respiratory Tract Infections  1  5/140 (3.57%)  4/159 (2.52%)  7/152 (4.61%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 9.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
No publication related to study results will be published prior to publication of a multi-center report submitted for publication within 18 months after conclusion or termination of a study. Results publications will be submitted to sponsor for review 60 days in advance of publication. Sponsor can require removal of confidential information unrelated to study results. Sponsor can embargo a proposed publication for another 60 days to preserve intellectual property.
Results Point of Contact
Name/Title: Sr. VP Clinical Sciences
Organization: Takeda Global Research and Development Center, Inc.
Phone: 800-778-2860
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00255151     History of Changes
Other Study ID Numbers: T-EE04-087
U1111-1114-1767 ( Registry Identifier: WHO )
First Submitted: November 15, 2005
First Posted: November 17, 2005
Results First Submitted: February 20, 2009
Results First Posted: August 28, 2009
Last Update Posted: February 3, 2012