Double-blind, randomised, placebo-controlled, phase IIa trial on the efficacy and tolerability of an 8-week treatment with two different doses of budesonide orodispersible tablets vs. placebo for prevention of oesophageal strictures in adult patients after endoscopic submucosal dissection

Inclusion criteria:
1. Signed informed consent;
2. Male or female patients, 18 to 85 years of age;
3. Estimated life expectancy of at least one year (not applicable in Portugal);
4. ECOG Performance Status of <= 2 at the randomisation visit (i.e. after the
ESD-procedure);
5. a) Biopsy proven or endoscopically suspect oesophageal SCC and/or high grade
dysplasia in a focal lesion of the squamous epithelium, treated with ESD;
or
b) Biopsy proven or endoscopically suspect BE-HGD or EAC, treated with ESD;
6. Mucosal defect after ESD of
a) >= 50% oesophageal circumference in a patient with SCC,
or
b) >= 75% oesophageal circumference in a patient with BE-HGD or EAC;
7. Negative pregnancy test in females of childbearing potential at the
screening visit;
8. Women of childbearing potential agree to apply during the entire duration of
the trial an effective method of birth control, which is defined as those,
which result in a low failure rate (i.e., less than 1% per year) when used
constantly and correctly. Such methods include implants, injectables, combined
oral contraceptive method, combined contraceptive patches and vaginal rings,
copper containing IUDs, sexual abstinence, or vasectomised partner. The
investigator is responsible for determining whether the patient applies
adequate birth control methods to allow for trial participation. Women of
non-childbearing potential may be included if surgically sterile (tubal
ligation or hysterectomy) or post-menopausal with at least two years without
spontaneous menses.

Exclusion criteria: :
1. Any prior or intended chemotherapy for oesophageal cancer;
2. Any prior ESD in the area where ESD will be done;
3. Any prior or intended oesophageal surgery or surgery for the mediastinum,
endoscopic mucosal resection (EMR), or radio frequency ablation (RFA), in the
area where ESD will be done;
4. Evidence of regional lymph node metastases or distant metastases prior to
ESD;
5. Any prior or intended radiotherapy which involves or affects the area of ESD
during the last 5 years;
6. Any prior endoscopic dilation for oesophageal stenosis which involves or
affects the area of ESD during the last 5 years;
7. Any other concomitant oesophageal disease (e.g. eosinophilic oesophagitis,
oropharyngeal or oesophageal bacterial, viral, or untreated or inadequately
treated fungal infection, inadequately treated candida oesophagitis or Zenker*s
diverticulum);
8. Achalasia, scleroderma oesophagus, or systemic sclerosis;
9. Necessity of oesophageal stent placement prior to randomisation;
10. Any known relevant infectious disease (e.g., AIDS defining diseases, active
tuberculosis);
11. Diagnosis of chickenpox, herpes zoster or measles within the last three
months prior to randomisation;
12. Known history of
a) liver cirrhosis,
b) severe renal impairment (Portugal only);
13. Any of the following medical conditions (if not being sufficiently under
control): cardiovascular disease, diabetes mellitus, osteoporosis, active
peptic ulcer disease, glaucoma, cataract;
14. Any severe concomitant disease, which in the opinion of the investigator
might have an influence on the patient*s compliance or the interpretation of
the results, or any disorder which in the opinion of the investigator might
affect the patient*s safety;
15. a) (All countries, except Portugal:) Any systemic therapy for any reason
that may affect assessment of primary or secondary endpoints, i.e., biologics,
or immunosuppressants, within the last 4 weeks prior to randomisation or
planned as concomitant treatment,
b) (Portugal only:) Any systemic therapy for any reason that may affect
assessment of primary or secondary endpoints, i.e., systemic
glucocorticosteroids, biologics, or immunosuppressants, within the last 4 weeks
prior to randomisation or planned as concomitant treatment;
16. a) (All countries, except Portugal:) Oral or intravenous systemic or oral
topical glucocorticosteroids for any reason that may affect assessment of
primary or secondary endpoints, which cannot be stopped at screening latest or
are planned as concomitant treatment;
b) (Portugal only:) Oral topical glucocorticosteroids used within the last 2
weeks prior to randomisation or planned as concomitant treatment;
17. Inhaled or nasal topical glucocorticosteroids for any reason that may
affect assessment of primary or secondary endpoints, which cannot be stopped at
screening latest or are planned as concomitant treatment for more than 7 days;
18. Any therapy with cytochrome P450 3A4 (CYP3A4) inhibitors which might
influence hepatic biotransformation: very potent (cobicistat, ritonavir,
ketoconazole, voriconazole), potent (boceprevir, clarithromycin, itraconazole,
saquinavir, telaprevir, telithromycin), or moderate (aprepitant, conivaptan,
diltiazem, erythromycin, fluconazole, nefazodone, posaconazole, verapamil)
administered repeatedly (i.e., > 3 days) in the last 3 weeks prior to
randomisation or planned as concomitant therapy for more than 7 days;
19. Any therapy with CYP3A4 inducers, which might influence hepatic
biotransformation: very potent (carbamazepine, phenytoin, rifampicin), moderate
(St. John*s Wort), administered repeatedly (i.e., > 3 days) in the last 3 weeks
prior to randomisation or planned as concomitant therapy for more than 7 days;
20. Live vaccination within the last 4 weeks prior to randomisation, or any
planned live vaccination during the trial;
21. Intake of grapefruit containing food or beverages during the DB treatment
phase;
22. Known intolerance/hypersensitivity/resistance to the investigational
medicinal product (IMP: budesonide) or its excipients or to drugs of similar
chemical structure or pharmacological profile;
23. History of intolerance/hypersensitivity to propofol (if propofol will be
used for sedation);
24. Well-founded doubt about the patient*s cooperation;
25. Existing or intended pregnancy or breast-feeding;
26. Participation in another clinical trial within the last 30 days prior to
the screening visit, simultaneous participation in another clinical trial, or
previous participation in the BUL-5 trial and having received any IMP.