E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects who have newly diagnosed or have a diagnosis of relapsing (relapses<to baseline) mild to moderate ulcerative colitis (UC). The original diagnosis of UC (total score of 4-10 on the Ulcerative Colitis Disease Activity Index and with a sigmoidoscopy score of >1 and a Physician Global Assessment of <2). The original diagnosis of UC must be established by sigmoidoscopy, colonoscopy, or barium enema and have compatible histology. |
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MedDRA Classification |
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 compare the percentage of subjects in remission after 8 weeks of treatment for the three treatment groups SPD476 2.4 g/day given twice daily and 4.8 g/day given once daily and placebo. Remission is defined as an Ulcerative Colitis Disease Activity Index (UC-DAI) score <1, with score of zero for rectal bleeding and stool frequency, and a sigmoidoscopy score reduction of 1 point or more from baseline. |
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E.2.2 | Secondary objectives of the trial |
- To compare the percentage of subjects achieving clinical improvement at week 8 as defined by a drop of >3 points from baseline in the overall UC-DAI score for the three treatment groups. - To compare the percentage subjects in remission after 8 week of treatment between two doses of SPD476. - To compare the change in the UC-DAI score from baseline to 8 week of treatment between the three treatment groups. - To compare the change in symptoms (rectal bleeding and stool frequency) from baseline to 2,4 and 8 weeks of treatment between the three treatment groups. - To compare the time to withdrawal between the 3 treatment groups. To compare the change in sigmoidoscopic (mucosal)appearance from baseline to 8 weeks of treatment between the 3 treatment groups. - To assess the safety and tolerability of SPD476 administered as 2.4 g/day given BID and 4.8 g/day given OD as compared to placebo. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
- Adults aged 18 and over, male and female -Women of childbearing potential must use an effective contraceptive method while the subject is on the study treatment and must agree to not become pregnant during 30 days after the last dose of the study drug. - Subject who are newly diagnosed or have diagnosis of relapsing mild to moderate UC. Diagnosis of UC originally must be established by sigmoidoscopy, colonoscopy, or barium enema and have compatible histology. - Subjects who, in the investigator's opinion are not likely to respond to 5-ASA doses of 2.4 g/day should not be included. |
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E.4 | Principal exclusion criteria |
-Severe UC according to the Physicians Global Asswssmant or subjects that have been in relapse for >6 weeks prior baselina. - Subjects who have relapsed on maintenance therapy with doses of 5-ASA>2g/day. If a subject had a recent 5-ASA dose reduction from >2g/day to <2g/day relapses within 2 weeks of thatv dose reduction, the subject will not be eligible . - Cron's Disease, proctitis, bleeding disorder, or active ulcer disease. -Subjects with Asthma if they are known to be 5-ASA sensitive. -Subjects who in the opinion of the investigator are at immediate or significant risk of toxic megacolon.¨ -Previous colon surgary. - Subjects with moderate or severe renal impairment (defined as a creatinine level of >2 mg/dl) are contra-indicated for the treatment with 5-ASA compounds |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint for this study is remission assessed by the UC-DAI score. It consists of 4 individual parameters (stool frequency, rectal bleeding, mucosal appearance and Physicians Global Assessment). All 4 parameters will be assessed individually on a scale from 0-3. Remission is defined as an UC-DAI score of <1, with score of zero for stool frequency and rectal bleeding and sigmoidoscopy score reduction of 1 point or more from baseline. Improvement of symptoms from baseline to 2,4, and 8 weeks will be assessed by using two individual parameters of the UC-DAI: stool frequency, rectal bleeding. Safety and tolerability will be assessed by adverse events, laboratory testing (hematology, biochemistry and urinalysis), physical examination and vital signs. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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.8.5 | The trial involves multiple Member States | No |
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 | Information not present in EudraCT |
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 |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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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Last visit of the last subject |
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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 | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |