E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Induction of remission in lymphocytic colitis |
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E.1.1.1 | Medical condition in easily understood language |
Improvement od the symptoms of lymphocytic colitis |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02] |
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 | 10025268 |
E.1.2 | Term | Lymphocytic colitis |
E.1.2 | System Organ Class | 100000004856 |
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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 |
The main objective of the trial is to compare the efficacy of 9 mg budesonide/day and 3 g mesalazine/day compared to placebo for the induction of remission in lymphocytic colitis |
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E.2.2 | Secondary objectives of the trial |
- To compare the efficacy of 3 g mesalazine/day vs. 9 mg budesonide/day for the induction of remission in lymphocytic colitis, - To study safety and tolerability of 9 mg budesonide/day and 3 g mesalazine/day vs. placebo in the form of adverse events and laboratory parameters, - To assess patients’ quality of life
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent, 2. Man or woman >/= 18 years to ≤ 90 years, 3. History of non-bloody, watery diarrhoea for at least 12 weeks prior randomisation in patients with newly diagnosed lymphocytic colitis, or history of clinical relapse for more than 1 week prior randomisation in patients with previously established lymphocytic colitis, 4. At least 28 stools within the last 7 days prior to baseline, thereof at least 20 watery/soft stools, 5. Complete colonoscopy (or proctosigmoidoscopy) within the last 12 weeks before screening, 6. Histologically confirmed diagnosis of lymphocytic colitis: a. > 20 intraepithelial lymphocytes (IELs)/100 epithelial cells, b. Signs of inflammation of the lamina propria, c. Normal (i.e., < 10 µm) sub-epithelial collagen layer on well-orientated sections, 7. Women of child-bearing potential have to apply during the enteric duration of the highly effective method of birth control, which is defined as those which result in alow failure rate( i. e. less than 1 % per year) when used constantly and correctly such as implants, injectables, combined oral contraceptive method, sexual abstinence or vasectomised partner. The investigator is responsible for determining whether the subject has adequate birth control for study participation.
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E.4 | Principal exclusion criteria |
1. Evidence of infectious diarrhoea (i.e., pathogenic bacteria in stool culture or rectal biopsies), 2. Diarrhoea as a result of the presence of other symptomatic organic disease(s) of the gastrointestinal tract or endoscopic-histological findings (i.e., collagenous colitis, ulcerative colitis, ischemic colitis, radiation colitis, Crohn’s disease, tumours, polyps > 2 cm), 3. Celiac disease (blood tests and/or oesophagogastroduodenoscopy with histological examination to be performed), 4. Suspicion of drug-induced lymphocytic colitis, 5. History of significant bowel resection, 6. History of radiation therapy towards the abdominal or pelvic region, 7. Post-diverticulitis stenosis, 8. Known hereditary problems of galactose or fructose intolerance, glucose-galactose malabsorption, sucrase-isomaltase insufficiency, Lapp lactase deficiency, or congenital lactase deficiency, 9. History of cancer in the last five years, 10. Severe co-morbidity substantially reducing life expectancy, 11. Abnormal hepatic function (ALT or ALP > 2.5 x upper limit of normal [ULN]), liver cirrhosis, or portal hypertension, 12. Abnormal renal function (Cystatin C > ULN), 13. Local intestinal infection, 14. Known established cataract, 15. Hemorrhagic diathesis, 16. Active peptic ulcer disease, 17. Asthma, diabetes mellitus, infection, osteoporosis, glaucoma, tuberculosis, or hypertension if careful medical monitoring is not ensured, 18. Any severe concomitant cardiovascular, renal, endocrine, or psychiatric disorder, 19. Known intolerance/hypersensitivity to study drugs or drugs of similar chemical structure or pharmacological profile, 20. Treatment with anti-diarrhoeals (e.g. loperamide), Boswellia serrata extract, cholestyramine. or bulking agents within the last 14 days before baseline, 21. Treatment with immunomodulators (e.g. azathioprine, 6-mercaptopurine, thioguanine or methotrexate) within 3 months before baseline, 22. Treatment with budesonide, mesalazine, steroids, or oral antibiotics within 4 weeks before baseline, 23. Doubt about the patient’s cooperation, e.g. because of addiction to alcohol or drugs, 24. Existing or intended pregnancy or breast-feeding, 25. Participation in another clinical trial within the last 30 days, simultaneous participation in another clinical trial, or previous participation in this trial.
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E.5 End points |
E.5.1 | Primary end point(s) |
Rate of clinical remission, defined as a maximum of 21 stools, thereof not more than 6 watery stools in the last 7 days prior the visit at week 8 (LOCF) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Patient Visit V5 after 8 weeks of treatment |
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E.5.2 | Secondary end point(s) |
Double-blinded phase: • Number (%) of patients with a maximum of 21 stools, thereof not more than 6 watery stools in the last 7 days prior the visit at week 2, 4, 6 and 8, • Number (%) of patients with a maximum of 21 stools in the last 7 days prior the visit at week 2, 4, 6, 8, and 8 (LOCF), • Number (%) of patients with a maximum of 6 watery stools in the last 7 days prior the visit at week 2, 4, 6, 8, and 8 (LOCF), • Number (%) of patients with baseline mean of > 3 stools/day, who have a mean of 3 stools/day AND a reduction of at least 1 stool from baseline in the last 7 days prior the visit at week 2, 4, 6, 6 (LOCF), 8, and 8 (LOCF), • Times to resolution of symptoms defined as the first of 7 consecutive days with: o 3 stools/day on average, or o < 1 watery stool/day on average, or o 3 stools/day on average, thereof < 1 watery stool/day on average • Impact on stool consistency (watery/soft/solid), • Impact on abdominal pain, • Impact on patient’s general well-being, • Proportion of patients being in histological remission at week 8 (LOCF) defined as 20 IELs/100 epithelial cells AND a reduction in lamina propria inflammation, • Proportion of patients with histological improvement at week 8 (LOCF) defined as a reduction of more than 50% of the number of IELs/100 epithelial cells compared to baseline and/or a reduction in lamina propria inflammation, • Proportion of patients with histological non-response (no significant change in IEL numbers, no change in lamina propria inflammation) at week 8 (LOCF), • Changes from baseline in histological parameters, • Severity of diarrhoea, • Number of days with diarrhoea (> 3 stools/day) in each week, • Number of days in each week with watery, soft, soft or solid, or solid stool consistency, respectively, • Average frequency of stools/day in each week, • Quality of life (by GIQLI, SHS) • Physician’s Global Assessment (PGA).
Open-label phase: • Number (%) of primary non-responders experiencing clinical remission, defined as a maximum of 21 stools, thereof not more than 6 watery stools in the last 7 days prior the visit at week 4 (LOCF) of the open-label phase, • Number (%) of patients with clinical relapse experiencing clinical remission, defined as a maximum of 21 stools, thereof not more than 6 watery stools in the last 7 days prior the visit at week 4 (LOCF) of the open-label phase, • Quality of life (by GIQLI, SHS).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Both MP are to be compared to placebo |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
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The study end is defined as “last patient out” (LPO) |
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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 | 0 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |