Efficacy and Tolerability of Budesonide Orodispersible Tablets in Preventing Esophageal Strictures Post-Endoscopic Submucosal Dissection in Adults
- Trial ID
- 2023-507897-42-00
- Protocol
- BUL-5/ESD
- Sponsor
- Dr. Falk Pharma GmbH
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to assess the **efficacy** of an eight-week treatment with budesonide orodispersible tablets, administered at doses of 2 x 1 mg/day or 2 x 2 mg/day, compared to placebo, for the prevention of oesophageal strictures in adult patients following endoscopic submucosal dissection. This is clinically relevant as oesophageal strictures can significantly impact a patient's quality of life and may require further medical interventions if not effectively managed.
Secondary objectives include:
- To study the **safety** and tolerability of budesonide orodispersible tablets versus placebo by evaluating adverse events and laboratory parameters.
- To assess patients' quality of life during the treatment period.
Participants
The clinical trial involves a total of **7 participants** who are adult patients aged between **18 to 85 years**. Both male and female subjects are included in the study, with a focus on the **prevention of oesophageal strictures** following endoscopic submucosal dissection. Participants were selected based on specific criteria, including an **ECOG Performance Status** of ≤ 2 and an estimated life expectancy of at least one year. The trial population includes individuals with biopsy-proven or endoscopically suspect oesophageal squamous cell carcinoma (SCC) or high-grade dysplasia, as well as those with Barrett's esophagus with high-grade dysplasia (BE-HGD) or esophageal adenocarcinoma (EAC), all treated with endoscopic submucosal dissection. Lifestyle considerations such as effective birth control methods are required for women of childbearing potential. The study does not provide additional information on the general health status or specific lifestyle habits of the participants.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, placebo-controlled, phase IIa study to evaluate the efficacy and tolerability of an 8-week treatment with two different doses of **budesonide** orodispersible tablets compared to placebo. The primary objective is to prevent oesophageal strictures in adult patients following endoscopic submucosal dissection. The trial will involve participants aged 18 to 85 years, with an estimated life expectancy of at least one year, and an ECOG Performance Status of ≤ 2 post-procedure. The study will commence with a screening visit to confirm eligibility based on inclusion criteria, such as biopsy-proven or endoscopically suspect oesophageal conditions treated with endoscopic submucosal dissection.
Participants will be randomly assigned to receive either 2 x 1 mg/day or 2 x 2 mg/day of budesonide orodispersible tablets or a placebo. The trial will span approximately 8 weeks, with the primary endpoint being the percentage of patients free of strictures at the 8-week visit. Secondary endpoints include the number of endoscopic dilations per patient during the double-blind treatment phase and the percentage of patients free of strictures until the follow-up visit. Study visits will include regular follow-up assessments to monitor the efficacy and safety of the treatment, with the final visit marking the end of the study. The expected duration of participant involvement is 8 weeks, with conditions for early termination including withdrawal of consent or adverse events compromising patient safety.
Treatment
The clinical trial involves the administration of **budesonide** in the form of effervescent tablets, identified as BUL03. The pharmaceutical form is an effervescent tablet, and the active substance is budesonide, originating from a chemical mixture. The maximum daily dose for BUL03 is 4.0 mg, with a total maximum dose of 4.0 mg over the treatment period. The administration route is oral, and the treatment duration is set for a maximum of 8 weeks. The medication is produced by DR. FALK PHARMA GMBH and is not a paediatric formulation. The dosing schedule involves administering the medication twice daily, with each dose being 2 mg.
Another experimental treatment in the trial is BUL02, also an effervescent tablet containing **budesonide**. Similar to BUL03, the active substance is derived from a chemical mixture. The maximum daily dose for BUL02 is 2.0 mg, with a total maximum dose of 2.0 mg over the treatment period. The administration route is oral, and the treatment duration is also set for a maximum of 8 weeks. This medication is also produced by DR. FALK PHARMA GMBH and is not a paediatric formulation. The dosing schedule involves administering the medication twice daily, with each dose being 1 mg.
The trial includes a placebo group, utilizing placebo orodispersible tablets. These tablets do not contain any active substance and serve as a comparator to evaluate the efficacy of the budesonide treatments. The placebo is administered orally, following the same dosing schedule as the experimental treatments, to maintain blinding and ensure the integrity of the trial results.
Efficacy
The efficacy of the clinical trial will be assessed by evaluating the prevention of **oesophageal strictures** in adult patients following endoscopic submucosal dissection. The primary endpoint for efficacy is the percentage of patients free of strictures at the visit during week 8. Secondary endpoints include the number of endoscopic dilations per patient during the double-blind treatment phase and the percentage of patients free of strictures until the follow-up visit.
The trial involves an 8-week treatment with two different doses of budesonide orodispersible tablets (2 x 1 mg/day or 2 x 2 mg/day) compared to placebo. Efficacy parameters will be collected and analyzed at specified timepoints, including the end of the treatment period at week 8. The assessment of these endpoints will be conducted through clinical evaluations and endoscopic procedures to determine the presence or absence of strictures.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Signed informed consent
- Male or female patients, 18 to 85 years of age
- Estimated life expectancy of at least one year (not applicable in Portugal);
- ECOG Performance Status of ≤ 2 at the randomisation visit (i.e. after the ESD-procedure);
- 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
- 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
- Negative pregnancy test in females of childbearing potential at the screening visit;
- 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
- Any prior or intended chemotherapy for oesophageal cancer;
- Any prior ESD in the area where ESD will be done;
- 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;
- Evidence of regional lymph node metastases or distant metastases prior to ESD;
- Any prior or intended radiotherapy which involves or affects the area of ESD during the last 5 yea
- Any prior endoscopic dilation for oesophageal stenosis which involves or affects the area of ESD during the last 5 years;
- 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);
- Achalasia, scleroderma oesophagus, or systemic sclerosis
- Necessity of oesophageal stent placement prior to randomisation;
- Any known relevant infectious disease (e.g., AIDS defining diseases, active tuberculosis);
- Diagnosis of chickenpox, herpes zoster or measles within the last three months prior to randomisation
- Known history of a) liver cirrhosis, b) severe renal impairment (Portugal only)
- Any of the following medical conditions (if not being sufficiently under control): cardiovascular disease, diabetes mellitus, osteoporosis, active peptic ulcer disease, glaucoma, cataract
- 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;
- 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
- 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
- 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;
- 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;
- 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;
- Live vaccination within the last 4 weeks prior to randomisation, or any planned live vaccination during the trial
- Intake of grapefruit containing food or beverages during the DB treatment phase
- Known intolerance/hypersensitivity/resistance to the investigational medicinal product (IMP: budesonide) or its excipients or to drugs of similar chemical structure or pharmacological profile;
- History of intolerance/hypersensitivity to propofol (if propofol will be used for sedation)
- Well-founded doubt about the patient’s cooperation
- Existing or intended pregnancy or breast-feeding;
- 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
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Recruiting | 13 May 2020 | 6 |
 Germany | Not Recruiting | 13 May 2020 | 22 |
 The Netherlands | Not Recruiting | 13 May 2020 | — |
 Poland | Not Recruiting | 13 May 2020 | 19 |
 Portugal | Not Recruiting | 13 May 2020 | 15 |
 Spain | Not Recruiting | 13 May 2020 | 4 |
 Sweden | Not Recruiting | 13 May 2020 | 6 |
| Netherlands | — | — | 21 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
BUL02 | Test | ORODISPERSIBLE TABLET | ORAL USE | 2.0 | 8 | PRD5759915 |
Placebo orodispersible tablets | Placebo | N/A | — | — | — | N/A |
BUL03 | Test | ORODISPERSIBLE TABLET | ORAL USE | 4.0 | 8 | PRD6821711 |