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A Study in Adolescents and Adults With Eosinophilic Esophagitis (EoE) Measuring Histologic Response and Determine if Reduction in Dysphagia is Achieved

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ClinicalTrials.gov Identifier: NCT02605837
Recruitment Status : Completed
First Posted : November 16, 2015
Results First Posted : March 16, 2020
Last Update Posted : June 8, 2021
Sponsor:
Information provided by (Responsible Party):
Takeda ( Shire )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Eosinophilic Esophagitis (EoE)
Interventions Drug: Oral Budesonide Suspension (OBS)
Drug: Placebo
Enrollment 318
Recruitment Details This study was conducted at 72 sites in North America from 07 December 2015 (first participant enrolled) to 15 February 2019 (last participant completed).
Pre-assignment Details A total of 318 participants were randomized and received the treatment (placebo or oral Budesonide suspension [OBS]) in a double blind fashion following a placebo lead-in phase and 296 participants completed the study.
Arm/Group Title Placebo Oral Budesonide Suspension (OBS)
Hide Arm/Group Description Participants received oral dose of 10 milliliter (ml) placebo matched with the Oral Budesonide Suspension (OBS) twice daily up to 16 weeks. Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Period Title: Overall Study
Started 105 213
Completed 94 202
Not Completed 11 11
Reason Not Completed
Adverse Event             3             1
Non-Compliance with Study Drug             0             1
Withdrawal by Subject             8             8
Physician Decision             0             1
Arm/Group Title Placebo Oral Budesonide Suspension (OBS) Total
Hide Arm/Group Description Participants received oral dose of 10 milliliter (ml) placebo matched with the Oral Budesonide Suspension (OBS) twice daily up to 16 weeks. Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks. Total of all reporting groups
Overall Number of Baseline Participants 105 213 318
Hide Baseline Analysis Population Description
Full analysis set (FAS) included all randomized participants who received at least one dose of a double-blind investigational product (IP).
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 105 participants 213 participants 318 participants
33.9  (12.13) 33.8  (11.89) 33.9  (11.95)
[1]
Measure Description: Age was calculated as the difference between date of birth and date of informed consent, truncated to years.
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 105 participants 213 participants 318 participants
Female
43
  41.0%
84
  39.4%
127
  39.9%
Male
62
  59.0%
129
  60.6%
191
  60.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 105 participants 213 participants 318 participants
Hispanic or Latino
2
   1.9%
8
   3.8%
10
   3.1%
Not Hispanic or Latino
100
  95.2%
204
  95.8%
304
  95.6%
Unknown or Not Reported
3
   2.9%
1
   0.5%
4
   1.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 105 participants 213 participants 318 participants
American Indian or Alaska Native
0
   0.0%
1
   0.5%
1
   0.3%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
1
   1.0%
0
   0.0%
1
   0.3%
Black or African American
0
   0.0%
5
   2.3%
5
   1.6%
White
101
  96.2%
200
  93.9%
301
  94.7%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
3
   2.9%
7
   3.3%
10
   3.1%
1.Primary Outcome
Title Number of Participants With Histologic Response at the Final Treatment Period Evaluation (Week 16)
Hide Description Histologic response was defined as a peak eosinophil count of less than or equal to (<=) 6/ high-powered field (HPF) across all available esophageal levels at final treatment period evaluation (Week 16). Histologic response after 12 weeks of double blind treatment at Week 16 was reported.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received at least one dose of a double-blind IP.
Arm/Group Title Placebo Oral Budesonide Suspension (OBS)
Hide Arm/Group Description:
Participants received oral dose of 10 milliliter (ml) placebo matched with the Oral Budesonide Suspension (OBS) twice daily up to 16 weeks.
Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Overall Number of Participants Analyzed 105 213
Measure Type: Count of Participants
Unit of Measure: Participants
Histology Response - Yes
1
   1.0%
113
  53.1%
Histology Response - No
104
  99.0%
100
  46.9%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Oral Budesonide Suspension (OBS)
Comments The Cochran-Mantel-Haenszel (CMH) adjusted difference in proportion with corresponding Newcombe confidence interval (CI) and odds ratio with corresponding CI were based on CMH test stratified by age group and diet restriction.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in proportion of responders
Estimated Value 0.52
Confidence Interval 95%
0.433 to 0.591
Estimation Comments [Not Specified]
2.Primary Outcome
Title Number of Participants With Dysphagia Symptom Response at the Final Treatment Period Evaluation (Week 16)
Hide Description Dysphagia symptom response was defined as greater than or equal to (>=) 30 percent (%) reduction in the Dysphagia Symptom Questionnaire (DSQ) combined score (questions 2+3). DSQ contained 4 questions, all participants used a diary, and responded to Questions 1 (did you eat solid food) and 2 (did food pass slowly or get stuck). If the participant's answer to Question 2 was 'No', the diary ended for that day. If a participant answered 'Yes', he/she advanced to Questions 3 (did you have to do anything to make the food go down or get relief) and 4 (extent to which the participant experienced pain while swallowing). DSQ score= ([sum of points from questions 2+3 in the daily DSQ]×14)/ Number of diaries reported with non-missing data. Dysphagia symptom response after 12 weeks of double blind treatment at Week 16 was reported.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received at least one dose of a double-blind IP.
Arm/Group Title Placebo Oral Budesonide Suspension (OBS)
Hide Arm/Group Description:
Participants received oral dose of 10 milliliter (ml) placebo matched with the Oral Budesonide Suspension (OBS) twice daily up to 16 weeks.
Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Overall Number of Participants Analyzed 105 213
Measure Type: Count of Participants
Unit of Measure: Participants
Dysphagia symptom response: Yes
41
  39.0%
112
  52.6%
Dysphagia symptom response: No
64
  61.0%
101
  47.4%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Oral Budesonide Suspension (OBS)
Comments The CMH adjusted difference in proportion with corresponding Newcombe confidence interval (CI) and odds ratio with corresponding CI were based on CMH test stratified by age group and diet restriction.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.024
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in proportion of responders
Estimated Value 0.13
Confidence Interval 95%
0.016 to 0.243
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Dysphagia Symptom Questionnaire (DSQ) Combined Score at the Final Treatment Period Evaluation (Week 16)
Hide Description DSQ contained 4 questions, all participants used a diary, and responded to Questions 1 (did you eat solid food) and 2 (did food pass slowly or get stuck). If the participant's answer to Question 2 was 'No', the diary ended for that day. If a participant answered 'Yes', he/she advanced to Questions 3 (did you have to do anything to make the food go down or get relief) and 4 (extent to which the participant experienced pain while swallowing). DSQ combined score= ([sum of points from questions 2+3 in the daily DSQ]×14)/ Number of diaries reported with non-missing data. Scale range was 0 - 2 for question 2 and 0 - 4 for question 3, with higher values representing a worse outcome. Scale range for DSQ combined score was 0 - 84, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased. Change from baseline in DSQ after 12 weeks of double blind treatment at Week 16 was reported.
Time Frame Baseline, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received at least one dose of a double-blind IP. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Arm/Group Title Placebo Oral Budesonide Suspension (OBS)
Hide Arm/Group Description:
Participants received oral dose of 10 milliliter (ml) placebo matched with the Oral Budesonide Suspension (OBS) twice daily up to 16 weeks.
Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Overall Number of Participants Analyzed 89 197
Least Squares Mean (Standard Error)
Unit of Measure: Score on scale
-9.07  (1.519) -12.99  (1.202)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Oral Budesonide Suspension (OBS)
Comments This analysis was from analysis of covariance (ANCOVA) model with treatment group and age group as factors and the baseline DSQ combined score as a continuous covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.015
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least square mean
Estimated Value -3.92
Confidence Interval 95%
-7.073 to -0.774
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Total Endoscopy Score at the Final Treatment Period Evaluation (Week 16)
Hide Description Endoscopic findings with separate evaluations of the proximal and distal esophagus were recorded with respect to 5 categories: 1) exudates or plaques (grade 0-2); 2) fixed esophageal rings (grade 0-3); 3) edema (grade 0-2); 4) furrows (grade 0-2); and 5) strictures (grade 0-1). An endoscopy score for each category was calculated and summed for each anatomic location (proximal and distal). The minimum and maximum endoscopy score was 0 and 10 points respectively for each location (proximal and distal) and the total endoscopy score was the sum of the scores for the proximal and distal locations (maximum total score of 20 points respectively). The higher score indicated worse appearance. A negative change from baseline indicates that appearance improved. Endoscopic findings after 12 weeks of double blind treatment at Week 16 were reported.
Time Frame Baseline, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received at least one dose of a double-blind IP. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Arm/Group Title Placebo Oral Budesonide Suspension (OBS)
Hide Arm/Group Description:
Participants received oral dose of 10 milliliter (ml) placebo matched with the Oral Budesonide Suspension (OBS) twice daily up to 16 weeks.
Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Overall Number of Participants Analyzed 93 202
Least Squares Mean (Standard Error)
Unit of Measure: score on scale
-2.2  (0.38) -4.0  (0.30)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Oral Budesonide Suspension (OBS)
Comments This analysis was from analysis of covariance (ANCOVA) model with treatment group and age group as factors and the baseline. Total EREFS (endoscopy score) as a continuous covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least square mean
Estimated Value -1.8
Confidence Interval 95%
-2.6 to -1.1
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Number of Participants With Peak Eosinophil Count Less Than (<)15/High-Powered Field (HPF) or Less Than or Equal to (<=)1/High-Powered Field (HPF) at the Final Treatment Period Evaluation (Week 16)
Hide Description Participant was considered as responder at Week 16 if he/she had peak eosinophil count of <15/HPF or <=1/HPF across all esophagus levels. Number of participants with peak eosinophil count < 15/HPF or <=1/HPF after 12 weeks of double blind treatment at Week 16 were reported.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received at least one dose of a double-blind IP.
Arm/Group Title Placebo Oral Budesonide Suspension (OBS)
Hide Arm/Group Description:
Participants received oral dose of 10 milliliter (ml) placebo matched with the Oral Budesonide Suspension (OBS) twice daily up to 16 weeks.
Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Overall Number of Participants Analyzed 105 213
Measure Type: Count of Participants
Unit of Measure: Participants
Peak Eosinophil Count (<15/HPF): Responders
1
   1.0%
132
  62.0%
Peak Eosinophil Count (<15/HPF): Non-responders
104
  99.0%
81
  38.0%
Peak Eosinophil Count (<=1/HPF): Responders
0
   0.0%
69
  32.4%
Peak Eosinophil Count (<=1/HPF): Non-responders
105
 100.0%
144
  67.6%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Oral Budesonide Suspension (OBS)
Comments Peak eosinophil count (<15/HPF) was performed based on logistic regression model adjusted for age group and diet restriction.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 169.74
Confidence Interval 95%
23.235 to 1239.979
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Oral Budesonide Suspension (OBS)
Comments Peak eosinophil count (<=1/HPF) was performed based on firth logistic regression model adjusted for age group and diet restriction.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Firth logistic regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 100.69
Confidence Interval (2-Sided) 95%
6.294 to 1610.749
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in the Peak Eosinophil Count at the Final Treatment Period Evaluation (Week 16)
Hide Description Change from baseline in the peak eosinophil count after 12 weeks of double blind treatment at week 16 for each available esophageal level (proximal, mid, distal, maximum) were reported.
Time Frame Baseline, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received at least one dose of a double-blind IP. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure at each specific category.
Arm/Group Title Placebo Oral Budesonide Suspension (OBS)
Hide Arm/Group Description:
Participants received oral dose of 10 milliliter (ml) placebo matched with the Oral Budesonide Suspension (OBS) twice daily up to 16 weeks.
Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Overall Number of Participants Analyzed 105 213
Least Squares Mean (Standard Error)
Unit of Measure: eosinophil count
Proximal: Week 16 Number Analyzed 92 participants 201 participants
-5.5  (3.19) -34.0  (2.52)
Mid: week 16 Number Analyzed 92 participants 199 participants
-12.9  (3.74) -43.3  (3.01)
Distal: Week 16 Number Analyzed 91 participants 201 participants
-4.9  (3.66) -38.0  (2.88)
Maximum: Week 16 Number Analyzed 92 participants 201 participants
-7.6  (4.27) -55.2  (3.37)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Oral Budesonide Suspension (OBS)
Comments This analysis of proximal eosinophil count was from the analysis of covariance (ANCOVA) model with treatment group and age group as factors and the baseline Peak Eosinophil Count as a continuous covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least square mean
Estimated Value -28.4
Confidence Interval 95%
-35.0 to -21.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Oral Budesonide Suspension (OBS)
Comments This analysis of mid eosinophil count was from the analysis of covariance (ANCOVA) model with treatment group and age group as factors and the baseline Peak Eosinophil Count as a continuous covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least square mean
Estimated Value -30.4
Confidence Interval 95%
-38.1 to -22.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Oral Budesonide Suspension (OBS)
Comments This analysis of distal eosinophil count was from the analysis of covariance (ANCOVA) model with treatment group and age group as factors and the baseline Peak Eosinophil Count as a continuous covariate
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least square mean
Estimated Value -33.1
Confidence Interval 95%
-40.7 to -25.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Oral Budesonide Suspension (OBS)
Comments This analysis of maximum eosinophil count was from the ANCOVA model with treatment group and age group as factors and the baseline Peak eosinophil count as a continuous covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Mean
Estimated Value -47.6
Confidence Interval (2-Sided) 95%
-56.4 to -38.8
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in the Histopathologic Epithelial Features Combined Total Score Ratio (TSR) at the Final Treatment Period Evaluation (Week 16)
Hide Description Change from baseline in histopathologic epithelial features combined total score of grade and stage ratio after 12 weeks of double blind treatment at Week 16 were reported by measuring eight histopathologic epithelial features: basal layer hyperplasia, eosinophil density, eosinophil micro-abscesses, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, lamina propria fibrosis were scored on a 4-point scale (0=normal, 3=worst) for both the severity of the abnormality (grade) and the amount of tissue affected by the abnormality (stage). Thus each of the 3 levels had a minimum score of 0 and maximum possible score of 24, and a possible total grade or stage score of 72 for a maximum combined score of 144. Combined total score ratio (TSR) =(proximal TSR + mid TSR + distal TSR)/N, where N is the number of non missing sections for TSR. A negative change from baseline indicates that epithelial inflammation decreased.
Time Frame Baseline, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received at least one dose of a double-blind IP. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Arm/Group Title Placebo Oral Budesonide Suspension (OBS)
Hide Arm/Group Description:
Participants received oral dose of 10 milliliter (ml) placebo matched with the Oral Budesonide Suspension (OBS) twice daily up to 16 weeks.
Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Overall Number of Participants Analyzed 92 201
Least Squares Mean (Standard Error)
Unit of Measure: score on scale
Grade - Combined TSR: Week 16 -0.03  (0.016) -0.22  (0.013)
Stage - Combined TSR: Week 16 -0.0  (0.02) -0.2  (0.01)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Oral Budesonide Suspension (OBS)
Comments This analysis of histopathologic epithelial features combined grade TSR was from the analysis of covariance (ANCOVA) model with treatment group and age group as factors and the baseline Peak Eosinophil Count as a continuous covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least square mean
Estimated Value -0.19
Confidence Interval 95%
-0.22 to -0.16
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Oral Budesonide Suspension (OBS)
Comments This analysis of histopathologic epithelial features combined stage TSR was from the analysis of covariance (ANCOVA) model with treatment group and age group as factors and the baseline Peak Eosinophil Count as a continuous covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least square mean
Estimated Value -0.2
Confidence Interval 95%
-0.2 to -0.2
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Number of Participants With Dysphagia Symptom Response (Binary Response) at the Final Treatment Period Evaluation (Week 16)
Hide Description Dysphagia symptom response (binary response [i.e, responders versus. non-responders]) was defined as a >=50% reduction in the DSQ combined score (questions 2+3), from baseline to the final treatment period evaluation (Week 16). DSQ contained 4 questions, all participants used a diary, and responded to Questions 1 (did you eat solid food) and 2 (did food pass slowly or get stuck). If the participant's answer to Question 2 was 'No', the diary ended for that day. If a participant answered 'Yes', he/she advanced to Questions 3 (did you have to do anything to make the food go down or get relief) and 4 (extent to which the participant experienced pain while swallowing). DSQ score= ([sum of points from questions 2+3 in the daily DSQ]×14)/ Number of diaries reported with non-missing data. Number of participants with binary response after 12 weeks of double blind treatment at Week 16 were reported.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received at least one dose of a double-blind IP.
Arm/Group Title Placebo Oral Budesonide Suspension (OBS)
Hide Arm/Group Description:
Participants received oral dose of 10 milliliter (ml) placebo matched with the Oral Budesonide Suspension (OBS) twice daily up to 16 weeks.
Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Overall Number of Participants Analyzed 105 213
Measure Type: Count of Participants
Unit of Measure: Participants
Responders
35
  33.3%
88
  41.3%
Non Responders
70
  66.7%
125
  58.7%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Oral Budesonide Suspension (OBS)
Comments Dysphagia symptom response (binary response) at the final treatment period was performed based on logistic regression model adjusted for age group and diet restriction.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.164
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.42
Confidence Interval (2-Sided) 95%
0.866 to 2.333
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Number of Participants With Overall Binary Response I at the Final Treatment Period Evaluation (Week 16)
Hide Description Overall binary response I was defined as a reduction in the DSQ score of >=30% from baseline to the final treatment period (week 16) evaluation and a peak eosinophil count of <=6/HPF across all esophageal levels at the final treatment period evaluation. Participant was considered as responder at Week 16 if he/she achieved a minimum of 30% reduction in DSQ combined score between baseline and Week 16 and has peak eosinophil count of <=6/HPF across all esophagus levels. Number of participants with overall binary response I after 12 weeks of double blind treatment at Week 16 were reported.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received at least one dose of a double-blind IP.
Arm/Group Title Placebo Oral Budesonide Suspension (OBS)
Hide Arm/Group Description:
Participants received oral dose of 10 milliliter (ml) placebo matched with the Oral Budesonide Suspension (OBS) twice daily up to 16 weeks.
Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Overall Number of Participants Analyzed 105 213
Measure Type: Count of Participants
Unit of Measure: Participants
Overall Binary Response I: Responders
0
   0.0%
64
  30.0%
Overall Binary Response I: Non Responders
105
 100.0%
149
  70.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Oral Budesonide Suspension (OBS)
Comments Overall binary response I at the final treatment period was performed based on firth logistic regression model adjusted for age group and diet restriction.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Firth logistic regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 91.86
Confidence Interval (2-Sided) 95%
5.687 to 1483.680
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Number of Participants With Overall Binary Response II at the Final Treatment Period Evaluation (Week 16)
Hide Description Overall binary response II was defined as a reduction in the DSQ score of >=50% from baseline to the final treatment period evaluation and a peak eosinophil count of <=6/HPF across all esophageal levels at the final treatment period evaluation. Participant was considered as responder at Week 16 if he/she achieved a minimum of 50% reduction in DSQ combined score between baseline and Week 16 and had peak eosinophil count of <=6/HPF across all esophagus levels. Number of participants with overall binary response II after 12 weeks of double blind treatment at Week 16 were reported.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received at least one dose of a double-blind IP.
Arm/Group Title Placebo Oral Budesonide Suspension (OBS)
Hide Arm/Group Description:
Participants received oral dose of 10 milliliter (ml) placebo matched with the Oral Budesonide Suspension (OBS) twice daily up to 16 weeks.
Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Overall Number of Participants Analyzed 105 213
Measure Type: Count of Participants
Unit of Measure: Participants
Overall binary response II: Responders
0
   0.0%
48
  22.5%
Overall binary response II: Non-Responders
105
 100.0%
165
  77.5%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Oral Budesonide Suspension (OBS)
Comments Overall binary response II at the final treatment period was perfomed based on based on firth logistic regression model adjusted for age group and diet restriction.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Firth logistic regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 61.68
Confidence Interval (2-Sided) 95%
3.836 to 991.858
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change From Baseline in the Dysphagia Symptom Questionnaire (DSQ) + Pain Score (Questions 2 +3+4) at the Final Treatment Period Evaluation (Week 16)
Hide Description DSQ contained 4 questions, all participants used a diary, and responded to Questions 1 (did you eat solid food) and 2 (did food pass slowly or get stuck). If the participant's answer to Question 2 was 'No', the diary ended for that day. If a participant answered 'Yes', he/she advanced to Questions 3 (did you have to do anything to make the food go down or get relief) and 4 (extent to which the participant experienced pain while swallowing). DSQ + pain score was calculated by summing the scores of responses to questions 2, 3, and 4 by using following formula: DSQ + pain score= ([sum of points from questions 2+3+4 in the daily DSQ] ×14)/ Number of diaries reported with non-missing data. Scale range was 0 - 2 for question 2, 0 - 4 for question 3 and 0 - 4 for question 4, with higher values representing a worse outcome. Scale range for DSQ + pain score was 0 - 140, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased.
Time Frame Baseline, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received at least one dose of a double-blind IP. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Arm/Group Title Placebo Oral Budesonide Suspension (OBS)
Hide Arm/Group Description:
Participants received oral dose of 10 milliliter (ml) placebo matched with the Oral Budesonide Suspension (OBS) twice daily up to 16 weeks.
Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Overall Number of Participants Analyzed 89 197
Least Squares Mean (Standard Error)
Unit of Measure: Score on scale
-12.24  (2.097) -18.65  (1.660)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Oral Budesonide Suspension (OBS)
Comments This analysis was from the analysis of covariance (ANCOVA) model with treatment group and age group as factors and the baseline DSQ + Pain score as a continuous covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least square mean
Estimated Value -6.41
Confidence Interval 95%
-10.757 to -2.063
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Change From Baseline in the Dysphagia Symptom Questionnaire (DSQ) Pain Score (Question 4) at the Final Treatment Period Evaluation (Week 16)
Hide Description DSQ pain score was calculated by summing the scores of responses to Question 4 (extent to which the participant experienced pain while swallowing) only, by using the following formula: DSQ pain score= [(sum of points from question 4 in the daily DSQ)×14]/ Number of diaries reported with non-missing data. Scale range was 0 - 4 for question 4, with higher values representing a worse outcome. Scale range for DSQ pain score was 0 - 56, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased. Change from baseline in DSQ pain score (question 4) after 12 weeks of double blind treatment at Week 16 were reported.
Time Frame Baseline, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received at least one dose of a double-blind IP. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Arm/Group Title Placebo Oral Budesonide Suspension (OBS)
Hide Arm/Group Description:
Participants received oral dose of 10 milliliter (ml) placebo matched with the Oral Budesonide Suspension (OBS) twice daily up to 16 weeks.
Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Overall Number of Participants Analyzed 89 197
Least Squares Mean (Standard Error)
Unit of Measure: score on scale
-3.01  (0.751) -5.47  (0.595)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Oral Budesonide Suspension (OBS)
Comments This analysis was from the analysis of covariance (ANCOVA) model with treatment group and age group as factors and the baseline DSQ Pain score as a continuous covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least square mean
Estimated Value -2.46
Confidence Interval 95%
-4.018 to -0.909
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (AE)
Hide Description An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs were defined as AEs that start or deteriorate on or after the first dose of double-blind IP (Week 44) and through the safety follow-up contact, or 31 days after the last dose of IP for participants who did not have a safety follow-up contact. Number of participants with TEAE's were reported.
Time Frame From start of study drug administration up to follow-up (Week 20)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least one dose of any double-blind IP.
Arm/Group Title Placebo Oral Budesonide Suspension (OBS)
Hide Arm/Group Description:
Participants received oral dose of 10 milliliter (ml) placebo matched with the Oral Budesonide Suspension (OBS) twice daily up to 16 weeks.
Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Overall Number of Participants Analyzed 105 213
Measure Type: Count of Participants
Unit of Measure: Participants
64
  61.0%
130
  61.0%
14.Secondary Outcome
Title Area Under the Plasma Concentration-Time Curve (AUCtau) Between the Defined Interval of Budesonide Doses
Hide Description Area under the curve for the defined interval between doses (12 hours), calculated using the linear-up/log-down trapezoidal rule.The AUCtau of plasma budesonide was reported. Hours times pico grams per milliliter was abbreviated as h.pg/mL.
Time Frame Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Week 8, 12 and 16
Hide Outcome Measure Data
Hide Analysis Population Description
PK set included all participants in the safety set who received BOS treatment and provided at least one quantifiable plasma concentration of budesonide. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Arm/Group Title Oral Budesonide Suspension (OBS)
Hide Arm/Group Description:
Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Overall Number of Participants Analyzed 24
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h.pg/mL
5071
(58.1%)
15.Secondary Outcome
Title Maximum Observed Concentration (Cmax) of Budesonide in Plasma
Hide Description The Cmax of budesonide in plasma was reported.
Time Frame Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Week 8, 12 and 16
Hide Outcome Measure Data
Hide Analysis Population Description
PK set included all participants in the safety set who received BOS treatment and provided at least one quantifiable plasma concentration of budesonide. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Arm/Group Title Oral Budesonide Suspension (OBS)
Hide Arm/Group Description:
Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Overall Number of Participants Analyzed 47
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Picograms per milliliter (pg/mL)
914.8
(59.2%)
16.Secondary Outcome
Title Time to Maximum Observed Plasma Concentration (Tmax) of Budesonide in Plasma
Hide Description Tmax of budesonide in plasma was reported.
Time Frame Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Week 8, 12 and 16
Hide Outcome Measure Data
Hide Analysis Population Description
PK Set included all participants in the safety set who received BOS treatment and provided at least one quantifiable plasma concentration of budesonide. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Arm/Group Title Oral Budesonide Suspension (OBS)
Hide Arm/Group Description:
Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Overall Number of Participants Analyzed 47
Median (Full Range)
Unit of Measure: hour
2
(0.50 to 4)
17.Secondary Outcome
Title Terminal Rate Constant (Lambda Z) of Budesonide in Plasma
Hide Description Lambda Z of budesonide in plasma was reported.
Time Frame Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Week 8, 12 and 16
Hide Outcome Measure Data
Hide Analysis Population Description
PK set included all participants in the safety set who received BOS treatment and provided at least one quantifiable plasma concentration of budesonide. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Arm/Group Title Oral Budesonide Suspension (OBS)
Hide Arm/Group Description:
Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Overall Number of Participants Analyzed 23
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: per hour
0.2103
(25.2%)
18.Secondary Outcome
Title Terminal Half-Life (t1/2) of Budesonide in Plasma
Hide Description t1/2 of budesonide in plasma was reported
Time Frame Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Week 8, 12 and 16
Hide Outcome Measure Data
Hide Analysis Population Description
PK set included all participants in the safety set who received BOS treatment and provided at least one quantifiable plasma concentration of budesonide. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Arm/Group Title Oral Budesonide Suspension (OBS)
Hide Arm/Group Description:
Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Overall Number of Participants Analyzed 23
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour
3.296
(25.2%)
19.Secondary Outcome
Title Apparent Oral Clearance (CL/F) of Budesonide in Plasma
Hide Description CL/F of budesonide in plasma was reported.
Time Frame Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Week 8, 12 and 16
Hide Outcome Measure Data
Hide Analysis Population Description
PK set included all participants in the safety set who received BOS treatment and provided at least one quantifiable plasma concentration of budesonide. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Arm/Group Title Oral Budesonide Suspension (OBS)
Hide Arm/Group Description:
Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Overall Number of Participants Analyzed 24
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liter per hour (L/h)
394.4
(58.1%)
20.Secondary Outcome
Title Apparent Volume of Distribution (Vz/F) of Budesonide in Plasma
Hide Description Vz/F of budesonide in plasma was reported.
Time Frame Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Week 8, 12 and 16
Hide Outcome Measure Data
Hide Analysis Population Description
PK set included all participants in the safety set who received BOS treatment and provided at least one quantifiable plasma concentration of budesonide. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Arm/Group Title Oral Budesonide Suspension (OBS)
Hide Arm/Group Description:
Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Overall Number of Participants Analyzed 23
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liter (L)
1886
(51.4%)
Time Frame From start of study drug administration up to follow-up (Week 20)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Oral Budesonide Suspension (OBS)
Hide Arm/Group Description Participants received oral dose of 10 milliliter (ml) placebo matched with the Oral Budesonide Suspension (OBS) twice daily up to 16 weeks. Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
All-Cause Mortality
Placebo Oral Budesonide Suspension (OBS)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/105 (0.00%)      0/213 (0.00%)    
Hide Serious Adverse Events
Placebo Oral Budesonide Suspension (OBS)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/105 (0.95%)      2/213 (0.94%)    
Gastrointestinal disorders     
Localised intraabdominal fluid collection * 1  0/105 (0.00%)  0 1/213 (0.47%)  1
Infections and infestations     
Gastroenteritis * 1  0/105 (0.00%)  0 1/213 (0.47%)  1
Sepsis * 1  0/105 (0.00%)  0 1/213 (0.47%)  1
Reproductive system and breast disorders     
Ovarian cyst * 1  1/105 (0.95%)  1 0/213 (0.00%)  0
1
Term from vocabulary, MedDRA 18.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Placebo Oral Budesonide Suspension (OBS)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   28/105 (26.67%)      63/213 (29.58%)    
Gastrointestinal disorders     
Diarrhoea * 1  5/105 (4.76%)  5 2/213 (0.94%)  2
Nausea * 1  3/105 (2.86%)  3 6/213 (2.82%)  6
Oesophagitis * 1  0/105 (0.00%)  0 5/213 (2.35%)  5
Vomiting * 1  4/105 (3.81%)  6 4/213 (1.88%)  4
Infections and infestations     
Nasopharyngitis * 1  4/105 (3.81%)  6 11/213 (5.16%)  13
Oesophageal candidiasis * 1  2/105 (1.90%)  2 8/213 (3.76%)  8
Oral candidiasis * 1  0/105 (0.00%)  0 8/213 (3.76%)  9
Sinusitis * 1  3/105 (2.86%)  3 9/213 (4.23%)  9
Upper respiratory tract infection * 1  3/105 (2.86%)  3 4/213 (1.88%)  5
Injury, poisoning and procedural complications     
Procedural pain * 1  1/105 (0.95%)  1 5/213 (2.35%)  5
Investigations     
ACTH stimulation test abnormal * 1  3/105 (2.86%)  3 6/213 (2.82%)  7
Protein urine present * 1  3/105 (2.86%)  4 1/213 (0.47%)  1
Urine leukocyte esterase positive * 1  3/105 (2.86%)  4 0/213 (0.00%)  0
Nervous system disorders     
Headache * 1  1/105 (0.95%)  1 7/213 (3.29%)  7
Psychiatric disorders     
Insomnia * 1  3/105 (2.86%)  3 4/213 (1.88%)  5
Mood swings * 1  4/105 (3.81%)  4 3/213 (1.41%)  3
Respiratory, thoracic and mediastinal disorders     
Cough * 1  3/105 (2.86%)  3 6/213 (2.82%)  6
Skin and subcutaneous tissue disorders     
Acne * 1  3/105 (2.86%)  4 5/213 (2.35%)  5
Rash * 1  3/105 (2.86%)  4 2/213 (0.94%)  2
1
Term from vocabulary, MedDRA 18.0
*
Indicates events were collected by non-systematic assessment
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.
If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Shire
Phone: +1 866 842 5335
EMail: ClinicalTransparency@shire.com
Layout table for additonal information
Responsible Party: Takeda ( Shire )
ClinicalTrials.gov Identifier: NCT02605837    
Other Study ID Numbers: SHP621-301
First Submitted: November 4, 2015
First Posted: November 16, 2015
Results First Submitted: January 22, 2020
Results First Posted: March 16, 2020
Last Update Posted: June 8, 2021