Efficacy of Levocetirizine Fourfold Dosage in Chronic Spontaneous Urticaria

NCT ID: NCT02372604

Last Updated: 2018-09-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-31
• Study Completion Date: 2016-12-31

Brief Summary

Chronic Spontaneous Urticaria (CSU), defined by the persistence of daily or almost daily urticaria over 6 weeks, affects 0.5% to 1% of the general population. In more than half of the cases, it lasts more than 2 years. It can dramatically alter the quality of life, in particular sleep, and generates numerous consultations and hospitalizations, with an average annual cost per patient close to 2000 euros in Europe. The treatment is based on the validated 2nd generation anti-H1 antihistamines dosage of one tablet per day whose effectiveness is satisfactory, however about half the time. In cases of severe CSU refractory to treatment with anti-H1 licensed dosage, few therapeutic alternatives exist, still off-label: the monketulast, an anti-leukotriene, ciclosporine or methotrexate, as immunosuppressants. Various studies have shown the important benefit of an expensive anti-IgE biological: the omaluzimab. Several open studies have also suggested superior efficacy and good tolerability of anti-H1 in higher dosage (double, triple or quadruple) including levocetirizine.

The off-label use of these high dosages of anti-H1 is growing very rapidly in France, tending to replace the use of anti-H1 first generation or substitution to another 2nd generation anti-H1 recommended by the French Society of Dermatology.

This study, under the aegis of the Urticaria Group of the French Society of Dermatology, intends to compare the efficacy of levocetirizine 4 tablets/day versus 1 tablet/day in the treatment of CSU resistant to anti-H1 licensed dosage.

Conditions

Chronic Spontaneous Urticaria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Group1 : Regulatory dosage

In a first time, every day, one tablet of 5 mg of levocetirizine is taken the morning and a second tablet of placebo is taken the evening, during 5 weeks (between visit 2 and 3).

In a second time,and after primary endpoint assessment, every day, one tablet of 10 mg of levocetirizine is taken the morning and a second tablet of 10 mg of levocetirizine is taken the evening, during 5 weeks (between visit 3 and 4).

Group Type: ACTIVE_COMPARATOR

Levocetirizine (as levocetirizine dihydrochloride), 5mg ( then 20 mg) per day . Oral administration.

Intervention Type: DRUG

Week 1 to week 5, every day : - the morning : 5 mg of levocetirizine (capsule)

• the evening : placebo capsule

Week 6 to week 10, every day : - the morning : 10 mg of levocetirizine (capsule)

• the evening : 10 mg of levocetirizine (capsule))

Group 2 : fourfold dosage

In a first time, every day, one tablet of 10 mg of levocetirizine is taken the morning and a second tablet of 10 mg of levocetirizine is taken the evening, during 5 weeks (between visit 2 and 3).

In a second time, every day, one tablet of 5 mg of levocetirizine is taken the morning and a second tablet of placebo is taken the evening, during 5 weeks (between visit 3 and 4).

Group Type: EXPERIMENTAL

Levocetirizine, (as levocetirizine dihydrochloride) 20 mg ( then 5 mg) per day. Oral administration.

Intervention Type: DRUG

Week 1 to week 5, every day : - the morning : 10 mg of levocetirizine (tablet)

• the evening : 10 mg of levocetirizine(tablet)

Week 6 to week 10, every day : - the morning : 5 mg of levocetirizine (tablet)

• the evening : placebo tablet

Interventions

Levocetirizine (as levocetirizine dihydrochloride), 5mg ( then 20 mg) per day . Oral administration.

Week 1 to week 5, every day : - the morning : 5 mg of levocetirizine (capsule)

• the evening : placebo capsule

Week 6 to week 10, every day : - the morning : 10 mg of levocetirizine (capsule)

• the evening : 10 mg of levocetirizine (capsule))

Intervention Type: DRUG

Levocetirizine, (as levocetirizine dihydrochloride) 20 mg ( then 5 mg) per day. Oral administration.

Week 1 to week 5, every day : - the morning : 10 mg of levocetirizine (tablet)

• the evening : 10 mg of levocetirizine(tablet)

Week 6 to week 10, every day : - the morning : 5 mg of levocetirizine (tablet)

• the evening : placebo tablet

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Subject must be ≥18 years of age at screening.
• Chronic spontaneous urticaria already treated with anti-H1 for at least two months without sufficient efficacy.
• Urticaria Activity Score (UAS7) >12 at the randomization visit (visit 2).
• For female :

• Of childbearing potential: female must use an acceptable method of contraception during the period of 1 month before the inclusion to 1 month after the last study visit;
• Of non-childbearing potential: e.g. postmenopausal (absence of menstrual bleeding for 1 years), or having had a hysterectomy or bilateral ovariectomy or tubal ligation.
• Patient agrees not to take other treatments than those provided in the study.
• Willingness and ability to comply with the protocol requirements.
• Written informed consent given prior to any study-related procedure.
• Subject affiliated to the National Social Security System.

Exclusion Criteria

• Pregnancy, breastfeeding or planned pregnancy during the study.
• Inducible urticaria (except immediate dermographism associated with CSU)
• Differential diagnosis of CSU (urticarial vasculitis).
• Known hypersensitivity to antihistamine.
• Known hypersensitivity to one of the product components, to hydroxyzine or to piperazine derivative.
• Sleepiness disorders or with Epworth sleepiness scale >15.
• Treatment with systemic corticosteroids within the month before the screening visit.
• Treatment with montelukast within the week before the screening visit.
• Treatment with H2-antihistamine within the week before the screening visit.
• Treatment with immunosuppressive drugs (e.g. methotrexate, cyclosporine, azathioprine, mycophenolate mofetil …) within the month before the screening visit.
• Known congenital galactosemia, glucose and galactose malabsorption, lactase deficiency, or lactose and fructose intolerance.
• Swallowing disorders.
• Liver dysfunction with transaminase greater than twice the normal value.
• Renal failure with creatinine clearance <50mL/min (calculated by MDRD formula).
• Regular or excessive alcohol consumption.
• Unstabilized chronic disease under treatment.
• Subject protected by the law (adult under guardianship, or hospitalized in a public or private institution for a reason other than the study, or incarcerated).
• Subject with any additional condition that, in the opinion of the investigator, may interfere with the study assessment or put the subject at risk.
• Linguistic or mentally incapacity to sign the consent form.
• Subject in an exclusion period from a previous study or who is participating in another clinical trial

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Frédéric BERARD, Professor

Role: PRINCIPAL_INVESTIGATOR

Service d'Allergologie et Immunologie Clinique - Centre Hospitalier Universitaire Lyon Sud

Other Identifiers

2014.849

Identifier Type: -

Identifier Source: org_study_id