Trial Outcomes & Findings for Comparative Efficacy & Safety Study of D961H Versus Placebo for the Prevention of Gastric and Duodenal Ulcers With Low-dose Aspirin (NCT NCT01069939)
NCT ID: NCT01069939
Last Updated: 2012-11-22
Results Overview
Assessments for occurrence of gastric and/or duodenal ulcers were performed every 12 weeks after randomisation. The numbers of participants with recurrence of gastric and/or duodeal ulcers were analysed every 12 weeks up to 48 weeks.
COMPLETED
PHASE3
427 participants
From randomisation to up to 48 weeks (Maximum follow-up period at the interim analysis)
2012-11-22
Participant Flow
First participant enrolled on 4 February 2010. On 20 May 2011, the efficacy analysis was completed based on positive results of an interim analysis so that the efficacy data in this report are at the interim analysis. To evaluate the safety, the study was continued. The last participant completed the study on 9 November 2011.
Out of 914 enrolled participants, 430 participants were assigned , but 484 participants were not assigned. The major reasons of no assignment were 'Did not meet eligibility criteria' (462 participants) and 'Voluntary discontinuation by participant' (21 participants). After 366 participants were randomised, the interim analysis was done.
Participant milestones
| Measure |
Esomeprazole 20mg
Esomeprazole 20mg once daily oral
|
Placebo
Placebo once daily oral
|
|---|---|---|
|
Randomised and Included in the Analyses
STARTED
|
213
|
214
|
|
Randomised and Included in the Analyses
COMPLETED
|
164
|
137
|
|
Randomised and Included in the Analyses
NOT COMPLETED
|
49
|
77
|
|
At Data Cut Off Date (26 Feb 2011)
STARTED
|
213
|
214
|
|
At Data Cut Off Date (26 Feb 2011)
COMPLETED
|
182
|
182
|
|
At Data Cut Off Date (26 Feb 2011)
NOT COMPLETED
|
31
|
32
|
Reasons for withdrawal
| Measure |
Esomeprazole 20mg
Esomeprazole 20mg once daily oral
|
Placebo
Placebo once daily oral
|
|---|---|---|
|
Randomised and Included in the Analyses
Adverse Event
|
17
|
22
|
|
Randomised and Included in the Analyses
Withdrawal by Subject
|
15
|
12
|
|
Randomised and Included in the Analyses
Lost to Follow-up
|
1
|
1
|
|
Randomised and Included in the Analyses
Protocol Violation
|
0
|
1
|
|
Randomised and Included in the Analyses
Lack of Efficacy
|
0
|
1
|
|
Randomised and Included in the Analyses
Study-specific withdrawal criteria
|
7
|
33
|
|
Randomised and Included in the Analyses
Eligibility criteria not fulfilled
|
4
|
3
|
|
Randomised and Included in the Analyses
Use of prohibited concomitant drug
|
4
|
2
|
|
Randomised and Included in the Analyses
Physician Decision
|
0
|
2
|
|
Randomised and Included in the Analyses
Removal
|
1
|
0
|
Baseline Characteristics
Comparative Efficacy & Safety Study of D961H Versus Placebo for the Prevention of Gastric and Duodenal Ulcers With Low-dose Aspirin
Baseline characteristics by cohort
| Measure |
Esomeprazole 20mg
n=213 Participants
Esomeprazole 20mg once daily oral
|
Placebo
n=214 Participants
Placebo once daily oral
|
Total
n=427 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
<=64years
|
85 Participants
n=5 Participants
|
71 Participants
n=7 Participants
|
156 Participants
n=5 Participants
|
|
Age, Customized
Between 65 and 74 years
|
82 Participants
n=5 Participants
|
89 Participants
n=7 Participants
|
171 Participants
n=5 Participants
|
|
Age, Customized
>=75 years
|
46 Participants
n=5 Participants
|
54 Participants
n=7 Participants
|
100 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
43 Participants
n=5 Participants
|
46 Participants
n=7 Participants
|
89 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
170 Participants
n=5 Participants
|
168 Participants
n=7 Participants
|
338 Participants
n=5 Participants
|
|
Region of Enrollment
Taiwan
|
22 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
43 Participants
n=5 Participants
|
|
Region of Enrollment
Japan
|
160 Participants
n=5 Participants
|
160 Participants
n=7 Participants
|
320 Participants
n=5 Participants
|
|
Region of Enrollment
Korea, Republic of
|
31 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
64 Participants
n=5 Participants
|
|
Helicobacter pylori status
Positive
|
93 Participants
n=5 Participants
|
93 Participants
n=7 Participants
|
186 Participants
n=5 Participants
|
|
Helicobacter pylori status
Negative
|
117 Participants
n=5 Participants
|
116 Participants
n=7 Participants
|
233 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From randomisation to up to 48 weeks (Maximum follow-up period at the interim analysis)Population: Participants not taking investigational drug were not included. In total 364 participants were included in the efficacy evaluation at the interim analysis. 24 of the 364 total participants had an occurrence of gastric and/or duodenal ulcers by the 48-week assessment.
Assessments for occurrence of gastric and/or duodenal ulcers were performed every 12 weeks after randomisation. The numbers of participants with recurrence of gastric and/or duodeal ulcers were analysed every 12 weeks up to 48 weeks.
Outcome measures
| Measure |
Esomeprazole 20mg
n=182 Participants
Esomeprazole 20mg once daily oral
|
Placebo
n=182 Participants
Placebo once daily oral
|
|---|---|---|
|
Time From Randomization to Occurrence of Gastric and/or Duodenal Ulcers up to Data Cut-off Date for Interim Analysis.
0 - 12 weeks
|
1 Participants
|
16 Participants
|
|
Time From Randomization to Occurrence of Gastric and/or Duodenal Ulcers up to Data Cut-off Date for Interim Analysis.
13 - 24 weeks
|
1 Participants
|
4 Participants
|
|
Time From Randomization to Occurrence of Gastric and/or Duodenal Ulcers up to Data Cut-off Date for Interim Analysis.
25 - 36 weeks
|
0 Participants
|
2 Participants
|
|
Time From Randomization to Occurrence of Gastric and/or Duodenal Ulcers up to Data Cut-off Date for Interim Analysis.
37 - 48 weeks
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 48 weeks (Baseline to last measurement)Population: Participants who had LANZA scores at both baseline and post-dose were included into this analysis.
Modified Lanza scale attributes the degree of gastric mucosal lesion, graded on a 5 point scale (0=No hemorrhage, no erosion, 1=One hemorrhage or one erosions, 2=2-10 hemorrhages or erosions, 3=11-25 hemorrhages or erosions, 4=More than 25 hemorrhages or erosions, or ulcer). Higher scores indicate greater severity of gastric mucosal lesion.
Outcome measures
| Measure |
Esomeprazole 20mg
n=144 Participants
Esomeprazole 20mg once daily oral
|
Placebo
n=145 Participants
Placebo once daily oral
|
|---|---|---|
|
Change in Degree of Gastric Mucosal Lesion by Modified Lanza Scale From Baseline to Last Measurement up to Week 48
|
-0.4 Scores on a scale
Standard Deviation 0.6
|
1.3 Scores on a scale
Standard Deviation 1.6
|
SECONDARY outcome
Timeframe: 12, 24, 36 and 48 weeksPopulation: Patients with endoscopy were included in the analyses at 12, 24, 36 and 48 weeks after randomisation.
Endoscopy was conducted at 12, 24, 36 and 48 weeks after randomisation. At the endoscopy, participants was evaluated whether they have reflux esophagitis or not.
Outcome measures
| Measure |
Esomeprazole 20mg
n=141 Participants
Esomeprazole 20mg once daily oral
|
Placebo
n=138 Participants
Placebo once daily oral
|
|---|---|---|
|
Number of Participants With Reflux Esophagitis Evaluated by the LA Classification up to Week 48.
12 weeks
|
0 Participants
|
9 Participants
|
|
Number of Participants With Reflux Esophagitis Evaluated by the LA Classification up to Week 48.
24 weeks
|
1 Participants
|
6 Participants
|
|
Number of Participants With Reflux Esophagitis Evaluated by the LA Classification up to Week 48.
36 weeks
|
0 Participants
|
3 Participants
|
|
Number of Participants With Reflux Esophagitis Evaluated by the LA Classification up to Week 48.
48 weeks
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 48 weeks (Baseline to last measurement)Population: Participants who had the measurements of epigastric pain at baseline and post-dose up to 48 weeks were included in this analysis.
The severity of epigastric pain at baseline and the last measurement up to 48 weeks was obtained (None, Mild, Moderate, Severe). If the value at the last was better in a participant, the participant was categorized into "Improved". If the value was same, categorised into "Unchanged". If the value was worsened, categorise into "Worsened".
Outcome measures
| Measure |
Esomeprazole 20mg
n=168 Participants
Esomeprazole 20mg once daily oral
|
Placebo
n=172 Participants
Placebo once daily oral
|
|---|---|---|
|
Change in the Severity of Epigastric Pain From Baseline to Last Measurement up to Week 48
Improved
|
11 Participants
|
16 Participants
|
|
Change in the Severity of Epigastric Pain From Baseline to Last Measurement up to Week 48
Unchanged
|
153 Participants
|
145 Participants
|
|
Change in the Severity of Epigastric Pain From Baseline to Last Measurement up to Week 48
Worsened
|
4 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: Up to 48 weeks (Baseline to last measurement)Population: Participants who had the measurements of heartburn at baseline and post-dose up to 48 weeks were included in this analysis.
The severity of heartburn at baseline and the last measurement up to 48 weeks was obtained (None, Mild, Moderate, Severe). If the value at the last was better in a participant, the participant was categorized into "Improved". If the value was same, categorised into "Unchanged". If the value was worsened, categorise into "Worsened".
Outcome measures
| Measure |
Esomeprazole 20mg
n=168 Participants
Esomeprazole 20mg once daily oral
|
Placebo
n=172 Participants
Placebo once daily oral
|
|---|---|---|
|
Change in the Severity of Heartburn From Baseline to Last Measurement up to Week 48.
Improved
|
7 Participants
|
6 Participants
|
|
Change in the Severity of Heartburn From Baseline to Last Measurement up to Week 48.
Unchanged
|
158 Participants
|
154 Participants
|
|
Change in the Severity of Heartburn From Baseline to Last Measurement up to Week 48.
Worsened
|
3 Participants
|
12 Participants
|
SECONDARY outcome
Timeframe: Up to 48 weeks (Baseline to last measurement)Population: Participants who had the measurements of anorexia at baseline and post-dose up to 48 weeks were included in this analysis.
The severity of anorexia at baseline and the last measurement up to 48 weeks was obtained (None, Mild, Moderate, Severe). If the value at the last was better in a participant, the participant was categorized into "Improved". If the value was same, categorised into "Unchanged". If the value was worsened, categorise into "Worsened".
Outcome measures
| Measure |
Esomeprazole 20mg
n=168 Participants
Esomeprazole 20mg once daily oral
|
Placebo
n=172 Participants
Placebo once daily oral
|
|---|---|---|
|
Change in the Severity of Anorexia From Baseline to Last Measurement up to Week 48
Improved
|
9 Participants
|
10 Participants
|
|
Change in the Severity of Anorexia From Baseline to Last Measurement up to Week 48
Unchanged
|
156 Participants
|
153 Participants
|
|
Change in the Severity of Anorexia From Baseline to Last Measurement up to Week 48
Worsened
|
3 Participants
|
9 Participants
|
SECONDARY outcome
Timeframe: Up to 48 weeks (Baseline to last measurement)Population: Participants who had the measurements of abdomen enlarged feeling at baseline and post-dose up to 48 weeks were included in this analysis.
The severity of abdomen enlarged feeling at baseline and the last measurement up to 48 weeks was obtained (None, Mild, Moderate, Severe). If the value at the last was better in a participant, the participant was categorized into "Improved". If the value was same, categorised into "Unchanged". If the value was worsened, categorise into "Worsened".
Outcome measures
| Measure |
Esomeprazole 20mg
n=168 Participants
Esomeprazole 20mg once daily oral
|
Placebo
n=172 Participants
Placebo once daily oral
|
|---|---|---|
|
Change in the Severity of Abdomen Enlarged Feeling From Baseline to Last Measurement up to Week
Improved
|
18 Participants
|
24 Participants
|
|
Change in the Severity of Abdomen Enlarged Feeling From Baseline to Last Measurement up to Week
Unchanged
|
141 Participants
|
141 Participants
|
|
Change in the Severity of Abdomen Enlarged Feeling From Baseline to Last Measurement up to Week
Worsened
|
9 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: Up to 48 weeks (Baseline to last measurement)Population: Participants who had the measurements of Nausea and/or Vomiting at baseline and post-dose up to 48 weeks were included in this analysis.
The severity of Nausea and/or Vomiting at baseline and the last measurement up to 48 weeks was obtained (None, Mild, Moderate, Severe). If the value at the last was better in a participant, the participant was categorized into "Improved". If the value was same, categorised into "Unchanged". If the value was worsened, categorise into "Worsened".
Outcome measures
| Measure |
Esomeprazole 20mg
n=168 Participants
Esomeprazole 20mg once daily oral
|
Placebo
n=172 Participants
Placebo once daily oral
|
|---|---|---|
|
Change in the Severity of Nausea and/or Vomiting From Baseline to Last Measurement up to Week 48
Improved
|
8 Participants
|
5 Participants
|
|
Change in the Severity of Nausea and/or Vomiting From Baseline to Last Measurement up to Week 48
Unchanged
|
160 Participants
|
154 Participants
|
|
Change in the Severity of Nausea and/or Vomiting From Baseline to Last Measurement up to Week 48
Worsened
|
0 Participants
|
13 Participants
|
SECONDARY outcome
Timeframe: Up to 48 weeks (Baseline to last measurement)The severity of Discomfort in the stomach at baseline and the last measurement up to 48 weeks was obtained (None, Mild, Moderate, Severe). If the value at the last was better in a participant, the participant was categorized into "Improved". If the value was same, categorised into "Unchanged". If the value was worsened, categorise into "Worsened".
Outcome measures
| Measure |
Esomeprazole 20mg
n=168 Participants
Esomeprazole 20mg once daily oral
|
Placebo
n=172 Participants
Placebo once daily oral
|
|---|---|---|
|
Change in the Severity of Discomfort in the Stomach From Baseline to Last Measurement up to Week 48
Improved
|
13 Participants
|
15 Participants
|
|
Change in the Severity of Discomfort in the Stomach From Baseline to Last Measurement up to Week 48
Unchanged
|
150 Participants
|
148 Participants
|
|
Change in the Severity of Discomfort in the Stomach From Baseline to Last Measurement up to Week 48
Worsened
|
5 Participants
|
9 Participants
|
SECONDARY outcome
Timeframe: Up to 70 weeks at the longestPopulation: All participants who received any study drug were included in this analysis.
Participants who had at least adverse events (AE) which occurred after receiving study drug were counted.
Outcome measures
| Measure |
Esomeprazole 20mg
n=214 Participants
Esomeprazole 20mg once daily oral
|
Placebo
n=213 Participants
Placebo once daily oral
|
|---|---|---|
|
Number of Participants With Adverse Events
Adverse event
|
155 Participants
|
139 Participants
|
|
Number of Participants With Adverse Events
Adverse event (Frequency>=5%)
|
70 Participants
|
53 Participants
|
|
Number of Participants With Adverse Events
Death
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Serious adverse event other than death
|
17 Participants
|
15 Participants
|
|
Number of Participants With Adverse Events
Adverse event leading to discontinuation of study
|
17 Participants
|
22 Participants
|
|
Number of Participants With Adverse Events
Drug-related adverse event
|
31 Participants
|
29 Participants
|
|
Number of Participants With Adverse Events
Severe adverse event
|
7 Participants
|
10 Participants
|
Adverse Events
Esomeprazole 20mg
Placebo
Serious adverse events
| Measure |
Esomeprazole 20mg
n=214 participants at risk
Esomeprazole 20mg once daily oral
|
Placebo
n=213 participants at risk
Placebo once daily oral
|
|---|---|---|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/214
|
0.47%
1/213
|
|
Surgical and medical procedures
Cholecystectomy
|
0.47%
1/214
|
0.00%
0/213
|
|
Respiratory, thoracic and mediastinal disorders
Sleep Apnoea Syndrome
|
0.47%
1/214
|
0.00%
0/213
|
|
Reproductive system and breast disorders
Epididymitis
|
0.47%
1/214
|
0.00%
0/213
|
|
Renal and urinary disorders
Renal Infarct
|
0.47%
1/214
|
0.00%
0/213
|
|
Musculoskeletal and connective tissue disorders
Intervertebral Disc Protrusion
|
0.47%
1/214
|
0.00%
0/213
|
|
Musculoskeletal and connective tissue disorders
Lumbar Spinal Stenosis
|
0.47%
1/214
|
0.00%
0/213
|
|
Investigations
Prostatic Specific Antigen Increased
|
0.47%
1/214
|
0.00%
0/213
|
|
Injury, poisoning and procedural complications
Hip Fracture
|
0.00%
0/214
|
0.47%
1/213
|
|
Injury, poisoning and procedural complications
In-Stent Coronary Artery Restenosis
|
0.47%
1/214
|
0.00%
0/213
|
|
Infections and infestations
Infective Exacerbation Of Chronic Obstructive Airways Disease
|
0.00%
0/214
|
0.47%
1/213
|
|
Infections and infestations
Pneumonia
|
0.00%
0/214
|
0.47%
1/213
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/214
|
0.47%
1/213
|
|
Infections and infestations
Urinary Tract Infection
|
0.47%
1/214
|
0.00%
0/213
|
|
Hepatobiliary disorders
Cholangitis Acute
|
0.47%
1/214
|
0.00%
0/213
|
|
Gastrointestinal disorders
Gastritis Erosive
|
0.00%
0/214
|
0.47%
1/213
|
|
Gastrointestinal disorders
Diverticulum Intestinal Haemorrhagic
|
0.00%
0/214
|
0.47%
1/213
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.47%
1/214
|
0.00%
0/213
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cardiac Myxoma
|
0.00%
0/214
|
0.47%
1/213
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung Neoplasm Malignant
|
0.00%
0/214
|
0.47%
1/213
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant Ascites
|
0.47%
1/214
|
0.00%
0/213
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric Cancer
|
0.47%
1/214
|
0.47%
1/213
|
|
Nervous system disorders
Epilepsy
|
0.00%
0/214
|
0.47%
1/213
|
|
Nervous system disorders
Cerebral Infarction
|
0.47%
1/214
|
0.00%
0/213
|
|
Nervous system disorders
Brain Stem Haemorrhage
|
0.93%
2/214
|
0.00%
0/213
|
|
Cardiac disorders
Ventricular Tachycardia
|
0.00%
0/214
|
0.47%
1/213
|
|
Cardiac disorders
Acute Myocardial Infarction
|
0.00%
0/214
|
0.94%
2/213
|
|
Cardiac disorders
Coronary Artery Stenosis
|
0.47%
1/214
|
0.00%
0/213
|
|
Cardiac disorders
Arteriosclerosis Coronary Artery
|
0.47%
1/214
|
0.00%
0/213
|
|
Cardiac disorders
Angina Pectoris
|
0.47%
1/214
|
0.47%
1/213
|
Other adverse events
| Measure |
Esomeprazole 20mg
n=214 participants at risk
Esomeprazole 20mg once daily oral
|
Placebo
n=213 participants at risk
Placebo once daily oral
|
|---|---|---|
|
Gastrointestinal disorders
Duodenitis
|
1.9%
4/214
|
5.2%
11/213
|
|
Gastrointestinal disorders
Gastric Polyps
|
5.1%
11/214
|
0.47%
1/213
|
|
Gastrointestinal disorders
Constipation
|
5.6%
12/214
|
5.2%
11/213
|
|
Infections and infestations
Nasopharyngitis
|
20.1%
43/214
|
14.1%
30/213
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee All PIs were prohibited to disclose all information related to this study without AZ approval before this study was completed.
- Publication restrictions are in place
Restriction type: OTHER