Efficacy of Rupatadine 5, 10 and 20 mg in Chronic Idiopathic Urticaria

A 4-week Dose-finding, Multicentre, Double-blind, Randomised, Placebo-controlled, Parallel-group Trial to Assess the Efficacy and Safety of Different Doses of Rupatadine Compared to Placebo in the Treatment of Chronic Idiopathic Urticaria

The objective of this study is to evaluate the efficacy and safety of rupatadine for the treatment of CIU symptoms.To assess the clinical efficacy of a dose ranging of rupatadine fumarate (5mg, 10mg, and 20 mg) compared with placebo for relief of CIU symptoms.

Objectives: To evaluate the efficacy and safety of rupatadine for the treatment of CIU symptoms.To assess the clinical efficacy of a dose ranging of rupatadine fumarate (5mg, 10mg, and 20 mg) compared with placebo for relief of CIU symptoms.

Methodology: A dose-finding multicentre, double-blind, randomised, placebo-controlled, parallel-group study Number of patients (planned and analysed): 248 patients. 62 patients will be allocated to each treatment group. 283 patients were randomised and analysed.

Diagnosis and criteria for inclusion: Man or woman aged between 12 and 65. Documented history of active CIU (urticaria wheals) with or without an associated angioedema for at least three days per week over the last 6 weeks prior to Day 0 . Active CIU (score ³2 labelled as moderate pruritus) for at least 3 days (not necessarily consecutive days) in the week before inclusion with a total score of active CIU ³6 labelled as moderate pruritus for these 3 days. Results of standard laboratory biochemistry and haematology tests obtained at screening within acceptable limits as assessed by investigator. Patient who signed the informed consent form.

Test product, dose, mode of administration, batch N°: Rupatadine 5,10 and 20 mg tablets; oral dose of 1 tablet/day for 4 consecutive weeks; batch 0102 (France) and batch 0203 (Hungary, Romania and Argentina). Expiry date: 12/2003 (France) and 10/2004 (Hungary, Romania and Argentina).

Duration of treatment: Oral administration of test formulation (5, 10, 20 mg) or placebo daily, for 4 consecutive weeks.

Reference therapy: Placebo tablets, 1 tablet/day for 4 consecutive weeks. Criteria for evaluation (efficacy): Primary efficacy measure of each treatment will compare the frequency and severity of symptoms of CIU as measured by the patient in terms of change in mean pruritus score (MPS) over the 4-week treatment period.Secondary efficacy measures include change from baseline over the 4-week treatment period in the mean number of wheals (MNW) score; mean total symptoms score (MTSS), calculated as the sum of the MPS (Mean pruritus symptoms) and the MNW (Mean number of wheals) scores and the interference with sleep and daily activities due to urticaria symptoms Criteria for evaluation (safety): AEs, laboratory tests and vital signs

Inclusion Criteria:

1. Man or woman aged between 12 and 65
2. Documented history of active CIU (urticaria wheals) with or without an associated angioedema for at least three days per week over the last 6 weeks prior to Day 0
3. Active CIU (score ³2 labelled as moderate pruritus) for at least 3 days (not necessarily consecutive days) in the week before inclusion with a total score of active CIU ³6 labelled as moderate pruritus for these 3 days
4. Results of standard laboratory biochemistry and haematology tests obtained at screening within acceptable limits as assessed by investigator
5. Patient who signed the informed consent form -

Exclusion Criteria:

1. CIU associated to some underlying disease (Hodgkin's disease/vasculitis/lupus erythematous/hepatitis)

2. Patient under any systemic or topical medication for CIU and/or an inferior wash-out period as stated as follows:

   • H1-receptor antagonists: fexofenadine (10 days prior to Day 0), loratadine, cetirizine, hydroxyzine, diphenhydramine, cyproheptadine, etc. (3 days prior to Day 0)
   • H2-receptor antagonists: cimetidine, ranitidine and famotidine (2 days prior to Day 0)
   • H1- and H2-receptor antagonists: doxepin (7 days prior to Day 0)
   • Leukotriene antagonists: zafirlukast and montelukast (4 days prior to Day 0)
   • Corticosteroids: prednisone and methylprednisolone (7 days prior to Day 0)
   • Tricyclic antidepressants: imipramin and amitriptilin (30 days prior to Day 0)

   The informed consent form must be signed prior to any washout period is set up.

3. Physical urticaria due to cold, heat, and/or sun

4. Cholinergic urticaria

5. Patient taking any potential inhibitors of the CYP3A4 isozyme of cytochrome P450 such as ketoconazole, erythromycin and/or tricyclic antidepressants, e.g. imipramin, amitriptilin, etc.

6. Urticaria due to known aetiology (e.g., medications, insects bites, food, etc)

7. Patient unresponsive to antihistaminic treatment

8. Patient with psychiatric disorders, vascular, hepatic, neurological, endocrine or other major systemic disease

9. Pregnant or lactating female

10. Patient with any heart abnormality of clinical relevance or any pathological changes of the heart rate

11. Patient under any medication which could interfere with drug effect or with interpretation of efficacy parameters

12. Subject handling dangerous machinery or driving as an integral part of his/her occupation

13. Patient with hereditary angioedema or isolated dermographism

14. Patient with disease caused by a parasite