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Efficacy and Safety of Dexlansoprazole MR Compared to Placebo on Maintaining Healing in Subjects With Healed Erosive Esophagitis

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ClinicalTrials.gov Identifier: NCT00321737
Recruitment Status : Completed
First Posted : May 4, 2006
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 445
Recruitment Details Subjects were enrolled at a total of 94 sites: 75 sites in the United States and 19 sites in Australia, Canada, the Czech Republic, Estonia, India, Latvia, Lithuania, Poland, and the Slovak Republic (date of first dose: 19 May 2006; date of last procedure: 21 May 2007).
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 30 mg QD Dexlansoprazole MR 60 mg QD
Hide Arm/Group Description Placebo capsules, orally, once daily for up to 6 months. Dexlansoprazole MR 30 mg, capsules, orally, once daily for up to 6 months. Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 6 months.
Period Title: Overall Study
Started 147 140 158
Completed 25 92 104
Not Completed 122 48 54
Reason Not Completed
Relapse of Erosive Esophagitis             76             25             19
Adverse Event             11             3             6
Lost to Follow-up             5             5             6
Withdrawal by Subject             19             12             17
Protocol Violation             0             0             1
Unmet Inclusion/Exclusion Criteria             1             0             0
Possible Barrett's Esophagus             2             1             1
Therapeutic Failure             6             0             2
Pregnancy             0             2             0
Noncompliance             2             0             0
Subject Request/ Subject Unavailable             0             0             2
Arm/Group Title Placebo QD Dexlansoprazole MR 30 mg QD Dexlansoprazole MR 60 mg QD Total
Hide Arm/Group Description Placebo capsules, orally, once daily for up to 6 months. Dexlansoprazole MR 30 mg, capsules, orally, once daily for up to 6 months. Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 6 months. Total of all reporting groups
Overall Number of Baseline Participants 147 140 158 445
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 147 participants 140 participants 158 participants 445 participants
49.5  (12.94) 47.1  (13.15) 47.9  (11.72) 48.2  (12.60)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 147 participants 140 participants 158 participants 445 participants
<45 years 50 54 58 162
45 - <65 years 83 75 89 247
≥65 years 14 11 11 36
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 147 participants 140 participants 158 participants 445 participants
Female
75
  51.0%
71
  50.7%
84
  53.2%
230
  51.7%
Male
72
  49.0%
69
  49.3%
74
  46.8%
215
  48.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 147 participants 140 participants 158 participants 445 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
4
   2.5%
4
   0.9%
Asian
3
   2.0%
3
   2.1%
5
   3.2%
11
   2.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
1
   0.6%
1
   0.2%
Black or African American
4
   2.7%
6
   4.3%
11
   7.0%
21
   4.7%
White
138
  93.9%
127
  90.7%
135
  85.4%
400
  89.9%
More than one race
1
   0.7%
4
   2.9%
2
   1.3%
7
   1.6%
Unknown or Not Reported
1
   0.7%
0
   0.0%
0
   0.0%
1
   0.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 147 participants 140 participants 158 participants 445 participants
Hispanic or Latino
20
  13.6%
21
  15.0%
19
  12.0%
60
  13.5%
Not Hispanic or Latino
127
  86.4%
119
  85.0%
139
  88.0%
385
  86.5%
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 147 participants 140 participants 158 participants 445 participants
A: ≥1 mucosal break <5 mm 51 53 56 160
B: ≥1 mucosal break ≥5 mm 57 46 57 160
C: ≥1 mucosal break <75% of circumference 34 31 39 104
D: ≥1 mucosal break ≥75% of circumference 5 10 6 21
[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 30 mg QD Dexlansoprazole MR 60 mg QD
Hide Arm/Group Description:
Placebo capsules, orally, once daily for up to 6 months.
Dexlansoprazole MR 30 mg, capsules, orally, once daily for up to 6 months.
Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 6 months.
Overall Number of Participants Analyzed 119 125 143
Measure Type: Number
Unit of Measure: Percentage of Subjects
14.3 66.4 66.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo QD, Dexlansoprazole MR 30 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 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 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Dexlansoprazole MR 30 mg 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 >0.99999
Comments Statistical significance was determined at the 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 30 mg QD Dexlansoprazole MR 60 mg QD
Hide Arm/Group Description:
Placebo capsules, orally, once daily for up to 6 months.
Dexlansoprazole MR 30 mg, capsules, orally, once daily for up to 6 months.
Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 6 months.
Overall Number of Participants Analyzed 145 137 153
Measure Type: Number
Unit of Measure: Percentage of Subjects
27.2 74.9 82.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo QD, Dexlansoprazole MR 30 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 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 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Dexlansoprazole MR 30 mg 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 0.13932
Comments Statistical significance was determined at the 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 30 mg QD Dexlansoprazole MR 60 mg QD
Hide Arm/Group Description:
Placebo capsules, orally, once daily for up to 6 months.
Dexlansoprazole MR 30 mg, capsules, orally, once daily for up to 6 months.
Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 6 months.
Overall Number of Participants Analyzed 141 132 147
Median (Inter-Quartile Range)
Unit of Measure: Percentage of Days
28.6
(5.9 to 61.8)
96.1
(80.7 to 100.0)
90.9
(66.7 to 99.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo QD, Dexlansoprazole MR 30 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 comparison 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 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 comparison 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 30 mg 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 0.06730
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 30 mg QD Dexlansoprazole MR 60 mg QD
Hide Arm/Group Description:
Placebo capsules, orally, once daily for up to 6 months.
Dexlansoprazole MR 30 mg, capsules, orally, once daily for up to 6 months.
Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 6 months.
Overall Number of Participants Analyzed 141 132 147
Mean (Standard Deviation)
Unit of Measure: Percentage of Days
36.0  (32.0) 83.3  (26.5) 78.4  (28.3)
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 30 mg QD Dexlansoprazole MR 60 mg QD
Hide Arm/Group Description:
Placebo capsules, orally, once daily for up to 6 months.
Dexlansoprazole MR 30 mg, capsules, orally, once daily for up to 6 months.
Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 6 months.
Overall Number of Participants Analyzed 140 132 147
Median (Inter-Quartile Range)
Unit of Measure: Percentage of Days
71.7
(19.5 to 92.2)
98.9
(90.9 to 100.0)
96.2
(80.0 to 100.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo QD, Dexlansoprazole MR 30 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 comparison of each 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 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 comparison of each 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 30 mg 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 0.11257
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 30 mg QD Dexlansoprazole MR 60 mg QD
Hide Arm/Group Description:
Placebo capsules, orally, once daily for up to 6 months.
Dexlansoprazole MR 30 mg, capsules, orally, once daily for up to 6 months.
Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 6 months.
Overall Number of Participants Analyzed 140 132 147
Mean (Standard Deviation)
Unit of Measure: Percentage of Days
57.7  (36.6) 89.3  (22.3) 86.0  (23.1)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo QD Dexlansoprazole MR 30 mg QD Dexlansoprazole MR 60 mg QD
Hide Arm/Group Description Placebo capsules, orally, once daily for up to 6 months. Dexlansoprazole MR 30 mg, capsules, orally, once daily for up to 6 months. Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 6 months.
All-Cause Mortality
Placebo QD Dexlansoprazole MR 30 mg QD Dexlansoprazole MR 60 mg QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo QD Dexlansoprazole MR 30 mg QD Dexlansoprazole MR 60 mg QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1   2   6 
General disorders       
Implant and Catheter Site Reactions  1  0/147 (0.00%)  0/140 (0.00%)  1/158 (0.63%) 
Pain and Discomfort Not Elsewhere Classified (NEC)  1  0/147 (0.00%)  0/140 (0.00%)  1/158 (0.63%) 
Hepatobiliary disorders       
Cholecystitis and Cholelithiasis  1  0/147 (0.00%)  0/140 (0.00%)  1/158 (0.63%) 
Infections and infestations       
Bacterial Infections NEC  1  0/147 (0.00%)  0/140 (0.00%)  1/158 (0.63%) 
Viral Infections NEC  1  0/147 (0.00%)  0/140 (0.00%)  1/158 (0.63%) 
Injury, poisoning and procedural complications       
Limb Injuries NEC (Including [Incl] Traumatic Amputation)  1  0/147 (0.00%)  0/140 (0.00%)  1/158 (0.63%) 
Non-Site Specific Injuries NEC  1  0/147 (0.00%)  0/140 (0.00%)  1/158 (0.63%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Prostatic Neoplasms Malignant  1  0/147 (0.00%)  1/140 (0.71%)  0/158 (0.00%) 
Nervous system disorders       
Cerebrovascular Venous and Sinus Thrombosis  1  0/147 (0.00%)  0/140 (0.00%)  1/158 (0.63%) 
Migraine Headaches  1  0/147 (0.00%)  0/140 (0.00%)  1/158 (0.63%) 
Pregnancy, puerperium and perinatal conditions       
Abortions Spontaneous  1  1/147 (0.68%)  1/140 (0.71%)  0/158 (0.00%) 
Reproductive system and breast disorders       
Ovarian And Fallopian Tube Cysts and Neoplasms  1  0/147 (0.00%)  0/140 (0.00%)  1/158 (0.63%) 
Uterine Disorders NEC  1  0/147 (0.00%)  0/140 (0.00%)  1/158 (0.63%) 
Respiratory, thoracic and mediastinal disorders       
Bronchospasm and Obstruction  1  0/147 (0.00%)  0/140 (0.00%)  1/158 (0.63%) 
Vascular disorders       
Peripheral Embolism and Thrombosis  1  0/147 (0.00%)  0/140 (0.00%)  1/158 (0.63%) 
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 30 mg QD Dexlansoprazole MR 60 mg QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   11   26   35 
Gastrointestinal disorders       
Diarrhoea (Excluding [Excl] Infective)  1  1/147 (0.68%)  5/140 (3.57%)  8/158 (5.06%) 
Gastritis (Excl Infective)  1  7/147 (4.76%)  2/140 (1.43%)  8/158 (5.06%) 
Infections and infestations       
Upper Respiratory Tract Infections  1  1/147 (0.68%)  14/140 (10.00%)  17/158 (10.76%) 
Musculoskeletal and connective tissue disorders       
Joint Related Signs and Symptoms  1  1/147 (0.68%)  7/140 (5.00%)  0/158 (0.00%) 
Musculoskeletal and Connective Tissue Signs and Symptoms NEC  1  2/147 (1.36%)  3/140 (2.14%)  8/158 (5.06%) 
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: NCT00321737     History of Changes
Other Study ID Numbers: T-EE05-135
2006-000419-90 ( EudraCT Number )
U1111-1113-9433 ( Registry Identifier: WHO )
First Submitted: May 2, 2006
First Posted: May 4, 2006
Results First Submitted: February 20, 2009
Results First Posted: August 28, 2009
Last Update Posted: February 3, 2012