E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045365 |
E.1.2 | Term | Ulcerative colitis |
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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 |
To evaluate the efficacy of CyCol (a controlled release minicapsule formaultion of ciclosporin) in inducing clinical remission, defined as a Disease Activity Index (DAI) score less than or equal to 2 after 4 weeks of treatment, in patients with mild to moderate ulcerative colitis (UC) involving at least the rectum and sigmoid colon, with no individual DAI sub-score >1 at week 4. Patients in remission by this definition will have a rectal bleeding DAI sub-score of either 0 or 1. |
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E.2.2 | Secondary objectives of the trial |
To evaluate further the efficacy of CyCol in this subject population based on the following: - mucosal healing - reduction in DAI score of less than or equal to 3 and with a decrease in the rectal bleeding sub-score of less than or equal to 1 or an absolute rectal bleeding sub-score of 0 or 1. - histological healing To evaluate safety and tolerability of CyCol in this subject population. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female subjects aged >18 years. 2. Subjects with a mild to moderate diagnosis of UC involving at least the rectum and sigmoid colon (i.e., ulcerative proctosigmoiditis, left-sided ulcerative colitis or pancolitis), determined by historical (> 3 months prior to Day 0) colonoscopy or, sigmoidoscopy, with biopsies.
3. Clinical severity assessed at screening using the Disease Activity Index (DAI, Table 1) of 4 to 10, inclusive, and must be restricted to either mild or moderate UC defined as:- Mild clinical disease — Subjects with mild clinical UC often present insidiously with intermittent rectal bleeding associated with the passage of mucus, and mild diarrhoea with fewer than 4 small loose stools per day. Mild crampy pain, tenesmus, and periods of constipation are also common, but severe abdominal pain, profuse bleeding, fever, and weight loss are not part of the spectrum of mild disease. - Moderate clinical disease — Subjects with moderate clinical disease have frequent loose, bloody stools (up to 8 per day), mild anaemia not requiring blood transfusions, abdominal pain that is not severe, and low grade fever. Adequate nutrition is usually maintained. 4. Clinical severity must be documented and confirmed by flexible sigmoidoscopy within 7 days of starting study treatment (i.e., Day 0)
5. Subjects must sign and date a written informed consent
6. Subjects must agree not to change the dosing regimen of any current UC medications (e.g. low dose steroids, e.g. < 10mg daily prednisolone, 5-ASA compounds, or immunomodulatory agents, namely purine analogues), starting at screening and continuining until the end of the 4-week treatment period of the study. 7. Subjects must agree to refrain from intake of St. Johns Wort or any other prescription, over-the-counter, or herbal preparation that is known to affect cytochrome P450 throughout the 4-week treatment period of the study. 8. Subjects must agree to refrain from intake of grapefruit or grapefruit juice or any other food or drink that is known to affect cytochrome P450 throughout the 4-week treatment period of the study. |
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E.4 | Principal exclusion criteria |
1. Subjects with severe or fulminant UC. 2. Subjects with UC limited to rectum only. 3. Subjects who have had any previous colonic surgery. 4. Subjects who have any histological evidence of dysplasia on colonoscopic biopsy. 5. Women of childbearing potential who are unable or unwilling to use an acceptable method of birth control to avoid pregnancy. 6. Subjects who have failed on previous ciclosporin therapy. 7. Subjects who have had any biologic therapy within the past 2 months prior to Day 0. 8. Subjects who have had methotrexate therapy within the past 6 months prior to Day 0. 9. Subjects who have had steroid treatment dose of greater than 10 mg/day prednisolone (or equivalent) within the past 2 months prior to Day 0. 10. Subjects who have had topical treatment (e.g. enemas) within 4 weeks of Day 0 and must refrain from taking topical treatments for UC from the screening visit until the end of the 4-week treatment period. 11. Subjects with renal impairment, hepatic impairment, uncontrolled hypertension, premalignant skin lesions or current malignancies or any other severe co-morbid condition. 12 Subjects with any known hypersensitivity to ciclosporin or any of its excipients. 13.Subjects with a positive screening stool assay for Clostridium difficile, hemorrhagic E.Coli 0157:H7, Salmonella or Shigella 14.Subjects with a diagnosis of Crohn’s colitis, ischemic colitis, NSAID-induced colitis, or radiation colitis.
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy: clinical remission defined as DAI score of less than or equal to 2 at Week 4 with no-individual DAI sub-score > 1 at week 4. Patients in remission by this definition will have a rectal bleeding DAI sub-score of either 0 or 1. |
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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 | No |
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 | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
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 | 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 | 20 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |