E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Induction of remission in active Crohn´s disease |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10058815 |
E.1.2 | Term | Crohn's disease acute episode |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011401 |
E.1.2 | Term | Crohn's disease |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary: • To evaluate the efficacy of 9 mg budesonide once daily (OD) vs. 3 mg budesonide three-times daily (TID) for the induction of remission in Crohn’s disease. |
|
E.2.2 | Secondary objectives of the trial |
Secondary: • To study safety and tolerability of 9 mg budesonide OD vs. 3 mg budesonide TID in the form of adverse events and laboratory parameters, • To evaluate the mucosal healing rate after 8-week treatment with budesonide, • To assess patients’ quality of life. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent, 2. Age 18 to 75 years, 3. Symptoms of Crohn’s disease since at least 3 months; diagnosis confirmed by endoscopic and histological, or endoscopic and radiological criteria [endoscopy not older than 12 months or if older, then clinical signs (e.g.,pain localisation, pain intensity, blood in stool) and behaviour (according to Montreal classification) should be unchanged compared to former episodes], 4. Localisation of CD either in terminal ileum, coecum, ascending colon, or ileocolitis, 5. Active phase of disease (200 < CDAI < 400), 6. Negative pregnancy test in females of childbearing potential, 7. Women of child-bearing potential have to apply appropriate contraceptive methods, e.g., hormonal contraception, intrauterine device (IUD), doublebarrier method of contraception (e.g., use of a condom and spermicide), or partner has undergone vasectomy. The investigator is responsible for determining whether the subject has adequate birth control for study participation. |
|
E.4 | Principal exclusion criteria |
1. Known Crohn’s lesions in the upper GI-tract (up to and including the jejunum) or rectum with present symptoms, 2. Septic complications, 3. Evidence of infectious diarrhoea (i.e., pathogenic bacteria in stool culture), 4. Abscess, perforation, or active fistulas, 5. Ileostomy or colostomy, 6. Resection of more than 50 cm of the ileum, 7. Bowel surgery within the last 3 months, 8. Immediate surgery required (e.g., major stenosis, serious bleeding, peritonitis, ileus), 9. Clinical signs of stricturing disease, 10. Subileus within the last 6 months (subileus with inflammatory hint allowed), 11. Suspicion of ileus, subileus or corresponding symptoms, 12. Parenteral or tube feeding, 13. Active peptic ulcer disease, local intestinal infection, or known established cataract, 14. Diabetes mellitus, infection, osteoporosis, glaucoma, tuberculosis, or hypertension if careful medical monitoring is not ensured, 15. Abnormal hepatic function (ALT or ALP > 2.5 x upper limit of normal [ULN]), liver cirrhosis, or portal hypertension, 16. Abnormal renal function (Cystatin C > ULN), 17. Any severe concomitant cardiovascular, renal, endocrine, or psychiatric disorder, 18. History of cancer in the last five years (except for non-metastatic cancers, e.g., basalioma), 19. Treatment with immunosuppressants or anti-cancer drugs, e.g., 6-TG, methotrexate, tacrolimus, cyclophosphamide, or cyclosporine within the last 3 months; in case of treatment with azathioprine or 6-MP the drugs have to be used for maintenance of remission only and dosage has to be unchanged within the last 3 months before baseline visit and during the study, 20. Treatment with ketoconazole or other CYP3A inhibitors within the last month before baseline visit, 21. Treatment with anti-TNF-α therapy within 3 months before baseline visit, 22. Conventional steroids (iv, po, rectal) within 2 weeks before baseline visit, 23. > 6 mg/d budesonide po within 2 weeks before baseline visit, 24. Steroids for inhalation within 2 weeks before baseline visit, 25. Patients known to be steroid-refractory, 26. Treatment of study disease with oral antibiotics (e.g., metronidazole or ciprofloxacin) within the last 2 weeks, 27. Application of non-steroidal anti-inflammatory drugs (NSAIDs) within 2 weeks before baseline visit except ≤ 350 mg/d or short-term acetylsalicylic acid (paracetamol is allowed), 28. Known intolerance/hypersensitivity to study drug, 29. Well-founded doubt about the patient’s cooperation, e.g., because of addiction to alcohol or drugs, 30. Existing or intended pregnancy or breast-feeding, 31. Participation in another clinical trial within the last 30 days, simultaneous participation in another clinical trial, or previous participation in this trial. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Rate of clinical remission, defined as a CDAI < 150, at week 8 (LOCF) |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Bulgaria |
Czech Republic |
Germany |
Hungary |
Latvia |
Lithuania |
Romania |
Russian Federation |
Slovakia |
Ukraine |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The study end is defined as “last patient out” (LPO), i.e., “last patient having his/her last visit”. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |