| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Mild to moderate active ulcerative colitis |
|
| 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 |
|
| 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 obtain first proof of clinical safety of dersalazine sodium at doses of 1200 mg given twice daily for 28 days in patients with mild to moderate active UC, as compared to placebo and active standard reference, mesalazine 1200 mg diven twice daily for 28 days. |
|
| E.2.2 | Secondary objectives of the trial |
- To obtain a rough assessment of the exposure to dersalazine and its metabolites (UR-12715, 5-ASA and N-acetyl-5-ASA) in a clinical setting in patients with mild to moderate active UC after repeated oral administration of 1200 mg doses twice daily for 28 days, by assessment of trough values at pre-dose and peak values post-dose.
- To explore the clinical activity of dersalazine sodium at doses of 1200 mg given twice daily for 28 days in patients with mild to moderate active UC, as compared to placebo and active standard reference (mesalazine). |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
- To assess the effect of dersalazine sodium at doses of 1200 mg given twice daily for 28 days on a set of markers of inflammatory activity in patients with mild to moderate active UC, as compared to placebo and active standard reference (mesalazine).
- To identify a set of biological parameters that might be used as markers of clinically relevant changes in inflammatory activity in patients with mild to moderate active UC in future clinical trials. |
|
| E.3 | Principal inclusion criteria |
1. Aged 18 to 65 years inclusive.
2. Patient is male or, if the patient is female, she is eligible to enter the study if she is of:
- Non-childbearing potential (i.e. physiologically incapable of becoming pregnant, including any female who has undergone sterilization or is post menopausal [1 year without menstruation])
OR
Child-bearing potential with the following restrictions:
- All females of child-bearing potential must have a negative serum pregnancy test immediately prior to enrolment
- All females of child-bearing potential, if heterosexually active, must be using an accepted form of contraception throughout the entire study period and for 1 monthly cycle following completion of the study. Accepted forms of contraception are defined as any hormonal contraception (for at least 2 monthly cycles prior to the start of the study), use of an intra-uterine device or male sterilisation plus usage by at least one of hte partners of an additional spermicidal-containing barrier method of contraception (condom or occlusive cap (diaphragm or cervical/vault caps)). The use of one contraception method alone or abstinence during the study period is not considered adequate.
3. A confirmed diagnosis of UC by endoscopy evaluation 3 months prior to entry into the study.
4. Disease extends at least 20 cm from the rectum on screening sigmoidoscopy.
5. Active UC as defined by a score between 5 and 10 inclusive in the Mayo score.
6. An endoscopy (flexible sigmoidoscopy) sub-score of at least 2 on the Mayo score determined within 10 days or less prior to first dosing.
7. Able to communicate well with the investigator and research staff and to comply with the requirements of the entire study.
8. Provision of written informed consent to participate in the study as shown by a signature on the patient consent form.
|
|
| E.4 | Principal exclusion criteria |
1. Patient has a significant medical condition, including psychiatric, which in the opinion of the investigator precludes participation in the study.
2. Patient has a history of allergy or intolerance to aspirin, mesalazine or other salicylates.
3. Patient has a faecal culture indicating the presence of pathogenic infection.
4. Patient has received immunosuppressive therapy (e.g. azathioprine, cyclosporine or mercaptopurine) within the last 90 days prior to screening.
5. Patient has received methotrexate within the last 90 days prior to screening.
6. Patient has received oral or i.v. corticosteroids within the last 30 days prior to screening (inhaled steroids are permitted).
7. Patient has been treated with biological therapy (e.g. infliximab, adalimumab, or natalizumab) within the last 90 days prior to screening.
8. Patient has received intra-rectal aminosalicilates or corticosteroirds within the last 14 days prior to screening.
9. Patient has received repeated treatment (more than 3 days) with non-steroidal anti-inflammatory drugs within the last 7 days prior to screening.
10. Patient has received antibiotics within the previous 14 days prior to screening.
11. Patient has participated in any investigational drug or device study within the 90 days prior to study screening.
12. Patient is pregnant, at risk of pregnancy, or is lactating.
13. Patient shows evidence of current excessive alcohol consumption or drug dependence in the opinion of the investigator.
14. Patient is unable to give his/her informed consent.
15. Patient is known to be positive for human immunodeficiency virus, hepatitis B virus, or hepatitis C virus.
16. Patient has other infectious, ischemic or immunologic disease.
17. Patient has values that are 2x ULN or greater for any of the following parameters: alanine aminotransferase (ALT/GOT), gamma glutamyl transferase (GGT), aspartate aminotransferase (AST/GPT), alkaline phosphatase (ALP) or total bilirubin (except isolated elevation or unconjugated bilirubin).
18. Patient has uncontrolled, clinically significant renal disease manifested by values that are 2x ULN or greater of serum creatinine or blood urea nitrogen (BUN) levels.
19. Patient has unstable cardiovascular disease (NYHA class III & IV coagulopathy or hypercoagulable state pulmonary disease - see protocol Appendix C for details).
20. Patient has any condition or circumstance that would, in the opinion of the investigator, prevent completion of the study or interfere with analysis of study results, including history of non-compliance with treatments or visits.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Proportion of patients with adverse events of severe intensity or adverse events leading to treatment withdrawal in each of the treatment groups. |
|
| 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 | Yes |
| 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 | Information not present in EudraCT |
| 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) | 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) | Yes |
| 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 | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 16 |
| 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
| |
| 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 | 9 |
| 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 |
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