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NCT01642212

OBS in Adolescent and Adults With EOE: A Phase II, Randomized, Double-Blind, Placebo Controlled, Study With an Open Label Extension

Completed Phase 2 Results posted Last updated 8 June 2021
What this trial tests

Phase 2 trial testing Oral Budesonide Suspension (MB-9) in Eosinophilic Esophagitis (EoE) in 93 participants. Completed in 30 October 2014.

Timeline
23 July 2012
Primary endpoint
30 October 2014
30 October 2014

Quick facts

Lead sponsorShire
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment93
Start date23 July 2012
Primary completion30 October 2014
Estimated completion30 October 2014
Sites23 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Shire — full company profile →

Who can join

Adults 11 to 40, any sex, with Eosinophilic Esophagitis (EoE). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percent of Participants Who Were Histologic Responders Primary · Week 16

Histologic response was defined as a peak eosinophil count \</= 6/high power field (light microscopy) (HPF) across all esophageal levels at the final treatment evaluation (Week 16). An independent, central pathologist determined the peak eosinophil count from the proximal, mid-, and distal levels and selected the maximum peak value. Histopathology data were collected in a blinded fashion.

GroupValue95% CI
Double-blind Placebo2.6
Double-blind Oral Budesonide Suspension (OBS) 2 mg38.8
Change From Baseline in The Dysphagia Symptom Questionnaire (DSQ) Score at The Final Treatment Period Evaluation Primary · Baseline, Week 16

Participants' dysphagia symptoms were evaluated using the 4-item DSQ. The questionnaire was developed by the Sponsor, as an ePRO measure, according to the principles of the Final Guidance for Industry for Patient Reported Outcome Measures (PRO Guidance December 2009). 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

GroupValue95% CI
Double-blind Placebo-7.53± 1.910
Double-blind Oral Budesonide Suspension (OBS) 2 mg-14.27± 1.682
Change From Baseline in The DSQ Score Over Time Secondary · Baseline, Weeks 8 and 12

Participants' dysphagia symptoms were evaluated using the 4-item DSQ. The questionnaire was developed by the Sponsor, as an ePRO measure, according to the principles of the Final Guidance for Industry for Patient Reported Outcome Measures (PRO Guidance December 2009). 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

Week 8, n = 37, 49
GroupValue95% CI
Double-blind Placebo-4.92± 1.673
Double-blind Oral Budesonide Suspension (OBS) 2 mg-7.41± 1.453
Week 12, n = 36, 49
GroupValue95% CI
Double-blind Placebo-7.42± 2.065
Double-blind Oral Budesonide Suspension (OBS) 2 mg-10.33± 1.770
Change From Baseline in The DSQ Score For The 50th Percentile of Participants at The Final Treatment Period Evaluation Secondary · Baseline, Week 16

A cumulative distribution function curve was constructed to illustrate the cumulative proportion of participants (x-axis) vs. the change in the DSQ score from baseline to the final treatment evaluation (y-axis). The 50th percentile is participants with a DSQ score that is in the middle of the distribution of all scores. A negative change from baseline indicates that symptoms decreased.

GroupValue95% CI
Double-blind Placebo-6.35
Double-blind Oral Budesonide Suspension (OBS) 2 mg-11.20
Percent of Participants With a Peak Eosinophil Count </= 15/High Power Field (Light Microscopy) (HPF) And </= 1/HPF at The Final Treatment Period Evaluation Secondary · Week 16

An independent, central pathologist determined the peak eosinophil count from the proximal, mid-, and distal levels and selected the maximum peak value across all available esophagus levels. Histopathology data were collected in a blinded fashion. The values reported are for participants with histologic response.

</= 15 Eosinophils/HPF
GroupValue95% CI
Double-blind Placebo7.9
Double-blind Oral Budesonide Suspension (OBS) 2 mg46.9
</= 1 Eosinophils/HPF
GroupValue95% CI
Double-blind Placebo0
Double-blind Oral Budesonide Suspension (OBS) 2 mg30.6
Percent of Participants With a >/= 30% And >/= 50% Reduction In The DSQ Score From Baseline to The Final Treatment Period Evaluation Secondary · Baseline, Week 16

Participants' dysphagia symptoms were evaluated using the 4-item DSQ. The questionnaire was developed by the Sponsor, as an ePRO measure, according to the principles of the Final Guidance for Industry for Patient Reported Outcome Measures (PRO Guidance December 2009). 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

>/= 30% DSQ Score Reduction
GroupValue95% CI
Double-blind Placebo44.7
Double-blind Oral Budesonide Suspension (OBS) 2 mg69.4
>/= 50% DSQ Score Reduction
GroupValue95% CI
Double-blind Placebo39.5
Double-blind Oral Budesonide Suspension (OBS) 2 mg63.3
Percent of Participants Who Were Overall Responders at The Final Treatment Period Evaluation Secondary · Week 16

Overall response was defined as a reduction in the 2-week DSQ score of \>/= 30% and \>/= 50% from baseline to the final treatment period evaluation and a peak eosinophil count of \</= 6/high power field (light microscopy) (HPF) across all available esophageal levels at the final treatment period evaluation. An independent, central pathologist determined the peak eosinophil count from the proximal, mid-, and distal levels and selected the maximum peak value. Histopathology data were collected in a blinded fashion.

Responder and >/= 30% DSQ Score Reduction
GroupValue95% CI
Double-blind Placebo2.6
Double-blind Oral Budesonide Suspension (OBS) 2 mg26.5
Responder and >/= 50% DSQ Score Reduction
GroupValue95% CI
Double-blind Placebo2.6
Double-blind Oral Budesonide Suspension (OBS) 2 mg20.4
Change From Baseline in The Histopathologic Epithelial Features Combined Total Score at The Final Treatment Period Evaluation Secondary · Baseline, Week 16

Each esophageal biopsy specimen was evaluated microscopically by an independent, central pathologist for signs of epithelial inflammation and lamina propria fibrosis. Histopathologic epithelial features of each available esophageal level biopsy consisting of basal layer hyperplasia, eosinophil peak, dilated intercellular spaces, eosinophil microabcesses, surface layering, surface alteration, and apoptotic epithelial cells were scored and summed. Histopathology data were collected in a blinded fashion. Histopathology epithelial features were scored for both grade and stage. Each feature had a p

GroupValue95% CI
Double-blind Placebo-1.41± 2.970
Double-blind Oral Budesonide Suspension (OBS) 2 mg-23.75± 2.602
Change From Baseline in The Total Endoscopy Score at The Final Treatment Period Evaluation Secondary · Baseline, Week 16

The gross endoscopic appearance of the esophageal surface was evaluated by a blinded study center physician. Endoscopic findings with separate evaluations of the proximal and distal esophagus were recorded with respect to 5 major categories, including exudates or plaques, fixed esophageal rings, edema, furrows, and strictures. The endoscopy score was the sum of the scores for the 5 major categories - grade 0-1 for strictures; grade 0-2 for exudates or plaques, edema, and furrows; and grade 0-3 for fixed esophageal rings for the proximal and distal locations. The maximum endoscopy score was 10

GroupValue95% CI
Double-blind Placebo0.19± 0.530
Double-blind Oral Budesonide Suspension (OBS) 2 mg-3.58± 0.466
Change From Baseline in The Peak Eosinophil Count at Each Available Esophageal Level at The Final Treatment Period Evaluation Secondary · Baseline, Week 16

An independent, central pathologist determined the peak eosinophil count from the proximal, mid-, and distal levels and selected the maximum peak value across all available esophagus levels. Histopathology data were collected in a blinded fashion. Baseline was defined as the score at screening. A negative change from baseline indicates that eosinophil count decreased.

Proximal, n = 32, 45
GroupValue95% CI
Double-blind Placebo-30.06± 6.798
Double-blind Oral Budesonide Suspension (OBS) 2 mg-65.56± 5.704
Mid-, n = 36, 46
GroupValue95% CI
Double-blind Placebo-17.34± 9.244
Double-blind Oral Budesonide Suspension (OBS) 2 mg-76.90± 8.173
Distal, n = 38, 49
GroupValue95% CI
Double-blind Placebo-1.90± 9.852
Double-blind Oral Budesonide Suspension (OBS) 2 mg-69.28± 8.667
Change From Baseline in The Physician's Global Assessment (PGA) of Disease Activity at The Final Treatment Period Evaluation Secondary · Baseline, Week 16

The physician Investigator (or qualified physician's assistant or nurse practitioner) completed the PGA to provide the global assessment of eosinophilic esophagitis (EoE) disease activity using a 0 to 100 mm visual analog scale (VAS) scale. The VAS is a 100 mm horizontal line on which the right extreme (100) is labeled "worst possible disease activity" and the left extreme (0) is labeled "no disease activity". The PGA raters were instructed to consider the line for the VAS a continuum with their own medical opinion or judgment of extremes on either end and to draw a vertical line at a point th

GroupValue95% CI
Double-blind Placebo-10.16± 4.199
Double-blind Oral Budesonide Suspension (OBS) 2 mg-28.61± 3.695
Distribution of Responses For The Patient Global Impression of Change (PGIC) Survey at The Final Treatment Evaluation Secondary · Week 16

Participants evaluated the change in their dysphasia (food passing slowly/difficulty swallowing) since the start of the study (screening) by choosing 1 of 7 responses on the PGIC survey: much worse (-3), worse (-2), a little worse (-1), no change (0), a little better (1), better (2), or much better (3). The values reported are the percent of participants who chose that response.

Much Worse
GroupValue95% CI
Double-blind Placebo0
Double-blind Oral Budesonide Suspension (OBS) 2 mg0
Worse
GroupValue95% CI
Double-blind Placebo2.6
Double-blind Oral Budesonide Suspension (OBS) 2 mg2.1
A Little Worse
GroupValue95% CI
Double-blind Placebo13.2
Double-blind Oral Budesonide Suspension (OBS) 2 mg2.1
No Change
GroupValue95% CI
Double-blind Placebo15.8
Double-blind Oral Budesonide Suspension (OBS) 2 mg12.5
A Little Better
GroupValue95% CI
Double-blind Placebo28.9
Double-blind Oral Budesonide Suspension (OBS) 2 mg25.0
Better
GroupValue95% CI
Double-blind Placebo28.9
Double-blind Oral Budesonide Suspension (OBS) 2 mg25.0
Much Better
GroupValue95% CI
Double-blind Placebo10.5
Double-blind Oral Budesonide Suspension (OBS) 2 mg33.3

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Double-blind Placebo
Serious: 0/42 (0%)
Deaths:
Double-blind Oral Budesonide Suspension (OBS) 2 mg
Serious: 1/51 (2%)
Deaths:
Placebo to Open-label Oral Budesonide Suspension (OBS) 2 mg
Serious: 1/37 (3%)
Deaths:
Oral Budesonide Suspension (OBS) 2 mg to Open-label OBS 2 mg
Serious: 0/45 (0%)
Deaths:

Serious adverse events (3 terms)

ReactionSystemDouble-blind PlaceboDouble-blind Oral Budesoni…Placebo to Open-label Oral…Oral Budesonide Suspension…
Food poisoningGastrointestinal disorders
Hand FractureInjury, poisoning and procedural complications
Road Traffic AccidentInjury, poisoning and procedural complications
Other adverse events (101 terms — click to expand)

ReactionSystemDouble-blind PlaceboDouble-blind Oral Budesoni…Placebo to Open-label Oral…Oral Budesonide Suspension…
NasopharyngitisInfections and infestations
Oesophageal candidiasisInfections and infestations
Upper respiratory tract infectionInfections and infestations
Wrist fractureInjury, poisoning and procedural complications
HeadacheNervous system disorders
AsthmaRespiratory, thoracic and mediastinal disorders
Food poisoningGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
PyrexiaGeneral disorders
Gastroenteritis viralInfections and infestations
InfluenzaInfections and infestations
SinusitisInfections and infestations
Viral infectionInfections and infestations
Vulvovaginal mycotic infectionInfections and infestations
Tendon ruptureInjury, poisoning and procedural complications
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
AcneSkin and subcutaneous tissue disorders
Dermatitis contactSkin and subcutaneous tissue disorders
LeukopeniaBlood and lymphatic system disorders
LymphadenopathyBlood and lymphatic system disorders
ArrhythmiaCardiac disorders
Ear discomfortEar and labyrinth disorders
VertigoEar and labyrinth disorders
GoitreEndocrine disorders
Abdominal discomfortGastrointestinal disorders
Abdominal painGastrointestinal disorders
Abdominal pain lowerGastrointestinal disorders
Breath odourGastrointestinal disorders
ConstipationGastrointestinal disorders
Diarrhoea haemorrhagicGastrointestinal disorders
DyspepsiaGastrointestinal disorders
Eosinophilic oesophagitisGastrointestinal disorders
Erosive oesophagitisGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
HaematocheziaGastrointestinal disorders
NauseaGastrointestinal disorders
Oesophageal food impactionGastrointestinal disorders
Oral painGastrointestinal disorders
StomatitisGastrointestinal disorders
ToothacheGastrointestinal disorders

Most-reported serious reactions: Food poisoning, Hand Fracture, Road Traffic Accident.

Data from ClinicalTrials.gov NCT01642212 adverse events section.

Sponsor's own description

This is a clinical trial to test an experimental drug for the treatment of Eosinophilic Esophagitis (EoE)

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Budesonide Oral Suspension Improves Symptomatic, Endoscopic, and Histologic Parameters Compared With Placebo in Patients With Eosinophilic Esophagitis.
    Dellon ES, Katzka DA, Collins MH, Hamdani M, et al · · 2017 · cited 179× · PMID 27889574 · DOI 10.1053/j.gastro.2016.11.021
  2. Safety and Efficacy of Budesonide Oral Suspension Maintenance Therapy in Patients With Eosinophilic Esophagitis.
    Dellon ES, Katzka DA, Collins MH, Gupta SK, et al · · 2019 · cited 59× · PMID 29902649 · DOI 10.1016/j.cgh.2018.05.051
  3. Psychometric validation of the Dysphagia Symptom Questionnaire in patients with eosinophilic esophagitis treated with budesonide oral suspension.
    Hudgens S, Evans C, Phillips E, Hill M. · · 2017 · cited 50× · PMID 29757322 · DOI 10.1186/s41687-017-0006-5
  4. Medical treatment of eosinophilic esophagitis.
    Franciosi JP, Gordon M, Sinopoulou V, Dellon ES, et al · · 2023 · cited 25× · PMID 37470293 · DOI 10.1002/14651858.cd004065.pub4
  5. Improvements in Dysphagia and Pain With Swallowing in Patients With Eosinophilic Esophagitis Receiving Budesonide Oral Suspension.
    Dellon ES, Collins MH, Katzka DA, Hudgens S, et al · · 2021 · cited 21× · PMID 32272243 · DOI 10.1016/j.cgh.2020.03.060
  6. Safety of an investigational formulation of budesonide (budesonide oral suspension) for eosinophilic oesophagitis: an integrated safety analysis of six phase 1-3 clinical trials.
    Hirano I, Dellon ES, Gupta SK, Katzka DA, et al · · 2023 · cited 16× · PMID 36890134 · DOI 10.1111/apt.17430
  7. A Pharmacokinetic Bridging Study to Compare Systemic Exposure to Budesonide between Budesonide Oral Suspension and ENTOCORT EC in Healthy Individuals.
    Song IH, Finkelman RD, Lan L. · · 2020 · cited 14× · PMID 33057953 · DOI 10.1007/s40268-020-00324-1
  8. Pooled Phase 2 and 3 Efficacy and Safety Data on Budesonide Oral Suspension in Adolescents with Eosinophilic Esophagitis.
    Mukkada VA, Gupta SK, Gold BD, Dellon ES, et al · · 2023 · cited 4× · PMID 37718471 · DOI 10.1097/mpg.0000000000003948

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Other recruiting trials for Eosinophilic Esophagitis (EoE)

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing