A double-blind, randomised, placebo and mesalazine controlled phase II study to explore the safety and activity of dersalazine in patients with mild to moderate active colitis

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2008-004610-27-BE
• Date of registration: 24/07/2008
• Prospective Registration: Yes
• Primary sponsor: Palau Pharma S.A.
• Public title: A double-blind, randomised, placebo and mesalazine controlled phase II study to explore the safety and activity of dersalazine in patients with mild to moderate active colitis
• Scientific title: A double-blind, randomised, placebo and mesalazine controlled phase II study to explore the safety and activity of dersalazine in patients with mild to moderate active colitis
• Date of first enrolment: 02/12/2008
• Target sample size: 90
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-004610-27
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

Belgium, Hungary, Spain

Key inclusion & exclusion criteria

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 the 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Mild to moderate active ulcerative colitis
MedDRA version: 9.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis

Intervention(s)

Product Name: Dersalazine sodium
Product Code: UR-12746-S
Pharmaceutical Form: Capsule*
INN or Proposed INN: dersalazine sodium
CAS Number: 367249-56-7
Current Sponsor code: UR-12746-S
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Trade Name: Lixacol
Product Name: Lixacol
Pharmaceutical Form: Over encapsulated tablet
INN or Proposed INN: Mesalazine
CAS Number: 89576
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Trade Name: Lixacol
Product Name: Lixacol
Pharmaceutical Form: Coated tablet
INN or Proposed INN: mesalazine
CAS Number: 89576
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-

Primary Outcome(s)

Main Objective: 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.

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.

Secondary Objective: - 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).

Secondary ID(s)

CR-IBD-1-08