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Compare D961H 20 mg Bid and 20 mg qd in Patients With Refractory Reflux Esophagitis (Inflammation of Lower Esophagus)

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ClinicalTrials.gov Identifier: NCT01669811
Recruitment Status : Completed
First Posted : August 21, 2012
Results First Posted : August 14, 2015
Last Update Posted : August 27, 2015
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Refractory Reflux Esophagitis
Interventions Drug: Esomeprazole (D961H) twice daily
Drug: Esomeprazole (D961H) once daily
Enrollment 1398
Recruitment Details First subject enrolled on 25 August 2012. Last subject completed on 30 May 2014.
Pre-assignment Details Out of 1398 enrolled subjects, 287 subjects were randomised and 1111 subjects were not randomised. The reasons of no randomisation were 'Eligibilty criteria not met' (1067 subjects), 'Subject decision' (37 subjects), 'Adverse event' (2 subjects) and other reasons (5 subjects).
Arm/Group Title D961H 20 mg BID D961H 20 mg QD + Placebo
Hide Arm/Group Description Hard capsule containing 22.3 mg of D961H as enteric coated pellets Hard capsule unidentifiable to D961H capsule 20 mg
Period Title: Overall Study
Started 145 142
Completed 142 131
Not Completed 3 11
Reason Not Completed
Investigator decision             0             1
Withdrawal by Subject             1             2
Adverse Event             2             6
Eligibility Criteria Not Fulfilled             0             2
Arm/Group Title D961H 20 mg BID D961H 20 mg QD + Placebo Total
Hide Arm/Group Description D961H 20 mg twice Daily D961H 20 mg once daily along with placebo Total of all reporting groups
Overall Number of Baseline Participants 145 140 285
Hide Baseline Analysis Population Description
It was found that 2 patients in D961H 20 mg QD + Placebo group had no refractory RE after randomisation. Therefore, these two patients were excluded from the full analysis set, which was the primary analysis set of this study and was used for summaries of baseline characteristics and outcome measures.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 145 participants 140 participants 285 participants
64.7  (13.87) 61.7  (14.72) 63.2  (14.35)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 145 participants 140 participants 285 participants
<65 68 69 137
>=65 77 71 148
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 145 participants 140 participants 285 participants
Female
69
  47.6%
70
  50.0%
139
  48.8%
Male
76
  52.4%
70
  50.0%
146
  51.2%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Asian Number Analyzed 145 participants 140 participants 285 participants
145 140 285
1.Primary Outcome
Title Percentage of Participants With Healing of RE Who Were Graded "O" at Week 8 Out of Participants Who Were Graded "A" to "D" at Baseline According to Los Angeles Classification
Hide Description Percentage of participants with healing of reflux esophagitis (RE) who were graded "O" (No RE) at Week 8 out of participants who were graded "A" (least severe) to "D" (most severe) at baseline according to Los Angeles classification
Time Frame 8 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Included all of the randomised participants who were definitely diagnosed to have refractory RE before the randomisation and who had at least one dose of investigational product
Arm/Group Title D961H 20mg Bid D961H 20mg QD + Placebo
Hide Arm/Group Description:
D961H 20mg twice daily
D961H 20mg once daily along with placebo
Overall Number of Participants Analyzed 145 140
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
92.4
(86.9 to 95.7)
68.6
(60.5 to 75.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection D961H 20mg Bid, D961H 20mg QD + Placebo
Comments To evaluate the efficacy of D20 bid on healing of refractory RE in comparison with D20 qd
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments p-value is obtained using chi square method.
Method Chi-squared
Comments 95% CI is obtained using Newcombe-Wilson score method without continuity correction.
Method of Estimation Estimation Parameter Difference in proportions
Estimated Value 23.8
Confidence Interval (2-Sided) 95%
14.9 to 32.6
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants With Healing of RE Who Were Graded "O" at Week 4 Out of Participants Who Were Graded "A" to "D" at Baseline According to Los Angeles Classification
Hide Description Percentage of participants with healing of reflux esophagitis (RE) who were graded "O" (No RE) at Week 4 out of participants who were graded "A" (least severe) to "D" (most severe) at baseline according to Los Angeles classification
Time Frame 4 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Included all of the randomised participants who were definitely diagnosed to have refractory RE before the randomisation and who had at least one dose of investigational product
Arm/Group Title D961H 20mg Bid D961H 20mg QD + Placebo
Hide Arm/Group Description:
D961H 20mg twice daily
D961H 20mg once daily along with placebo
Overall Number of Participants Analyzed 145 140
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
81.4
(74.3 to 86.9)
48.6
(40.4 to 56.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection D961H 20mg Bid, D961H 20mg QD + Placebo
Comments To evaluate the efficacy of D20 bid on healing of refractory RE in comparison with D20 qd
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments p-value is obtained using chi square method.
Method Chi-squared
Comments 95% CI is obtained using Newcombe-Wilson score method without continuity correction.
Method of Estimation Estimation Parameter Difference in proportions
Estimated Value 32.8
Confidence Interval (2-Sided) 95%
21.9 to 42.6
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Cumulative Percentage of Participants Who Had Sustained Resolution of GERD Symptom -Heartburn at Week 4
Hide Description Cumulative percentage of participants who had sustained resolution (defined as at least 7-day consecutive symptom free) of gastroesophageal reflux disease (GERD) symptom -heartburn at Week 4 (on Day 29) based on the Kaplan-Meier method.
Time Frame 4 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Included all of the randomised participants who were definitely diagnosed to have refractory RE before the randomisation and who took at least one dose of investigational product. However, out of these participants, only participants who had the GERD symptom -heartburn at baseline were included.
Arm/Group Title D961H 20mg Bid D961H 20mg QD + Placebo
Hide Arm/Group Description:
D961H 20mg twice daily
D961H 20mg once daily along with placebo
Overall Number of Participants Analyzed 90 81
Measure Type: Number
Unit of Measure: Percentage of participants
81.1 72.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection D961H 20mg Bid, D961H 20mg QD + Placebo
Comments To evaluate the efficacy of D20 bid on gastroesophageal reflux disease (GERD) symptoms in comparison with D20 qd
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1452
Comments [Not Specified]
Method Log Rank
Comments 95% CI of the hazard ratio is obtained using Cox proportional hazards model including a factor of treatment group.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.29
Confidence Interval (2-Sided) 95%
0.91 to 1.83
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Cumulative Percentage of Participants Who Had Sustained Resolution of GERD Symptom -Acid Regurgitation at Week 4
Hide Description Cumulative percentage of participants who had sustained resolution (defined as at least 7-day consecutive symptom free) of gastroesophageal reflux disease (GERD) symptom -acid regurgitation at Week 4 (on Day 29) based on the Kaplan-Meier method.
Time Frame 4 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Included all of the randomised participants who were definitely diagnosed to have refractory RE before the randomisation and who took at least one dose of investigational product. However, out of these participants, only participants who had the GERD symptom -acid regurgitation at baseline were included.
Arm/Group Title D961H 20mg Bid D961H 20mg QD + Placebo
Hide Arm/Group Description:
D961H 20mg twice daily
D961H 20mg once daily along with placebo
Overall Number of Participants Analyzed 78 67
Measure Type: Number
Unit of Measure: Percentage of participants
73.1 61.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection D961H 20mg Bid, D961H 20mg QD + Placebo
Comments To evaluate the efficacy of D20 bid on gastroesophageal reflux disease (GERD) symptoms in comparison with D20 qd
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0837
Comments [Not Specified]
Method Log Rank
Comments 95% CI of the hazard ratio is obtained using Cox proportional hazards model including a factor of treatment group.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.46
Confidence Interval (2-Sided) 95%
0.97 to 2.18
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Cumulative Percentage of Participants Who Had Sustained Resolution of GERD Symptom -Abdominal Pain at Week 4
Hide Description Cumulative percentage of participants who had sustained resolution (defined as at least 7-day consecutive symptom free) of gastroesophageal reflux disease (GERD) symptom -abdominal pain at Week 4 (on Day 29) based on the Kaplan-Meier method.
Time Frame 4 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Included all of the randomised participants who were definitely diagnosed to have refractory RE before the randomisation and who took at least one dose of investigational product. However, out of these participants, only participants who had the GERD symptom -abdominal pain at baseline were included.
Arm/Group Title D961H 20mg Bid D961H 20mg QD + Placebo
Hide Arm/Group Description:
D961H 20mg twice daily
D961H 20mg once daily along with placebo
Overall Number of Participants Analyzed 47 44
Measure Type: Number
Unit of Measure: Percentage of participants
68.1 59.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection D961H 20mg Bid, D961H 20mg QD + Placebo
Comments To evaluate the efficacy of D20 bid on gastroesophageal reflux disease (GERD) symptoms in comparison with D20 qd
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2678
Comments [Not Specified]
Method Log Rank
Comments 95% CI of the hazard ratio is obtained using Cox proportional hazards model including a factor of treatment group.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.34
Confidence Interval (2-Sided) 95%
0.80 to 2.26
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Cumulative Percentage of Participants Who Had Sustained Resolution of GERD Symptom -Difficulty of Swallowing at Week 4
Hide Description Cumulative percentage of participants who had sustained resolution (defined as at least 7-day consecutive symptom free) of gastroesophageal reflux disease (GERD) symptom -difficulty of swallowing at Week 4 (on Day 29) based on the Kaplan-Meier method.
Time Frame 4 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Included all of the randomised participants who were definitely diagnosed to have refractory RE before the randomisation and who took at least one dose of investigational product. However, out of these participants, only participants who had the GERD symptom -difficulty of swallowing at baseline were included.
Arm/Group Title D961H 20mg Bid D961H 20mg QD + Placebo
Hide Arm/Group Description:
D961H 20mg twice daily
D961H 20mg once daily along with placebo
Overall Number of Participants Analyzed 28 27
Measure Type: Number
Unit of Measure: Percentage of participants
78.6 74.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection D961H 20mg Bid, D961H 20mg QD + Placebo
Comments To evaluate the efficacy of D20 bid on gastroesophageal reflux disease (GERD) symptoms in comparison with D20 qd
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6389
Comments [Not Specified]
Method Log Rank
Comments 95% CI of the hazard ratio is obtained using Cox proportional hazards model including a factor of treatment group.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.15
Confidence Interval (2-Sided) 95%
0.62 to 2.12
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Cumulative Percentage of Participants Who Had Sustained Resolution of GERD Symptom -Sleep Disturbance at Week 4
Hide Description Cumulative percentage of participants who had sustained resolution (defined as at least 7-day consecutive symptom free) of gastroesophageal reflux disease (GERD) symptom -sleep disturbance at Week 4 (on Day 29) based on the Kaplan-Meier method.
Time Frame 4 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Included all of the randomised participants who were definitely diagnosed to have refractory RE before the randomisation and who took at least one dose of investigational product. However, out of these participants, only participants who had the GERD symptom -sleep disturbance at baseline were included.
Arm/Group Title D961H 20mg Bid D961H 20mg QD + Placebo
Hide Arm/Group Description:
D961H 20mg twice daily
D961H 20mg once daily along with placebo
Overall Number of Participants Analyzed 34 28
Measure Type: Number
Unit of Measure: Percentage of participants
91.2 89.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection D961H 20mg Bid, D961H 20mg QD + Placebo
Comments To evaluate the efficacy of D20 bid on gastroesophageal reflux disease (GERD) symptoms in comparison with D20 qd
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4485
Comments [Not Specified]
Method Log Rank
Comments 95% CI of the hazard ratio is obtained using Cox proportional hazards model including a factor of treatment group.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.38
Confidence Interval (2-Sided) 95%
0.80 to 2.38
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title D961H 20 mg BID D961H 20 mg QD + Placebo
Hide Arm/Group Description D961H 20 mg twice Daily D961H 20 mg once daily along with placebo
All-Cause Mortality
D961H 20 mg BID D961H 20 mg QD + Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
D961H 20 mg BID D961H 20 mg QD + Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/145 (0.69%)      3/142 (2.11%)    
Gastrointestinal disorders     
Gastritis  1  0/145 (0.00%)  0 1/142 (0.70%)  1
Gastrooesophageal reflux disease  1  0/145 (0.00%)  0 1/142 (0.70%)  1
Pancreatic pseudocyst  1  1/145 (0.69%)  1 0/142 (0.00%)  0
Infections and infestations     
Parotid abscess  1  0/145 (0.00%)  0 1/142 (0.70%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
D961H 20 mg BID D961H 20 mg QD + Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/145 (5.52%)      9/142 (6.34%)    
Infections and infestations     
Nasopharyngitis  1  8/145 (5.52%)  8 9/142 (6.34%)  9
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
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.
All PIs were prohibited to disclose all information related to this study withiout AZ approval before this study was completed.
Results Point of Contact
Name/Title: Masahiro Nii
Organization: Clinical Statistics & Programming Department, Clinical Science Division, R&D, AstraZeneca Japan
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01669811     History of Changes
Other Study ID Numbers: D961UC00002
First Submitted: August 17, 2012
First Posted: August 21, 2012
Results First Submitted: May 18, 2015
Results First Posted: August 14, 2015
Last Update Posted: August 27, 2015