Efficacy and Safety of Miltefosine in Antihistamine Resistant Chronic Urticaria
Condition: Chronic Urticaria
MeSH terms: Urticaria; Chronic Urticaria
Intervention: Miltefosine; Placebo
Intervention description: 50 or 100 or 150mg per day; Placebo
Intervention MeSH terms: Miltefosine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 76.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: urticaria

Summary:

      Randomised, double-blind, placebo-controlled study evaluating the effects of miltefosine on
      skin lesions in patients with treatment resistant chronic urticaria. Treatment resistance is
      defined by insufficient treatment response after a minimum of 1 week therapy with the maximum
      labelled dose of a non-sedating antihistamine. Eligible subjects will be enrolled at baseline
      8 (+/- 1) days after screening. 75 Patients will be randomised in a 2:1 ratio to one of the
      following treatment groups as add-on to the ongoing therapy with a non-sedating antihistamine
      for treatment period of 4 weeks: 25 placebo and 50 active drug Efficacy and safety
      evaluations are done at baseline day 7, 14, 21 safety, only) and 28 (or end of treatment) and
      at day 56 (28 days after end of treatment).
    

Eligibility criteria:

        Inclusion criteria Informed consent signed and dated Outpatients with moderate to severe
        spontaneous CU defined by UAS of ≥15 (under the maximum labelled dose of a non-sedating
        antihistamine Resistant to standard treatment with antihistamines after a minimum of 7 days
        therapy with the maximum labelled dose of a non-sedating antihistamine (levocetirizine,
        cetirizine, fexofenadine, desloratadine, loratadine, ebastine, mizolastine Aged more than
        18 years Reliable method of contraception for both women of childbearing potential as well
        as men during the study and 3 months thereafter. A highly effective method of birth control
        is defined as those which result in a low failure rate (i.e. less than 1% per year) when
        used consistently and correctly such as implants, injectables, combined oral
        contraceptives, some IUDs, sexual abstinence or vasectomised partner.

        Exclusion Criteria:

        Pregnancy or lactation Participation in another clinical trial within the last 30 days Body
        weight ≤ 45 kg Subjects who are inmates of psychiatric wards, prisons, or other state
        institutions. Existing or planned placement in an institution after ruling according to §
        40 passage 1 number 4 AMG (Arzneimittelgesetz).

        Skin symptoms caused primarily by physical urticaria Urticaria vasculitis Known
        hypersensitivity to miltefosine Retinal pathology Leishmaniasis Gastrointestinal
        disturbances which may influence oral resorption (e.g. chronic diarrhoea diseases,
        congenital malformations or major surgical resection of gastrointestinal tract).

        History within 5 years or presence of myocardial infarction or any other major cardiac
        disorder.

        Serum-creatinine and/or BUN 1.5 times above the upper reference value GOT and/or GPT and/or
        alkaline phosphatase 3 times above the upper reference value).

        Sjögren-Larsson-Syndrome. Malignancy within the last 5 years requiring chemotherapy or
        radiation therapy. Mental disorders that interfere with the evaluation of study end-points
        Drug or alcohol dependency Any other chronic or acute illness requiring systemic treatment
        which might have any influence on the outcome of the study in the 4 weeks before start of
        treatment and during the study (investigator's decision).

        Immunodeficiency including HIV During the past 10 days before start of treatment and during
        the study Topical steroids H2 antihistamines Leukotriene antagonists H1 antihistamine other
        then basic therapy During the past 2 weeks before start of treatment and during the study
        Ketotifen Doxepin During the past 4 weeks before start of treatment and during the study
        Systemic corticosteroids UV therapy including PUVA Systemic immunosuppressives including
        corticosteroids, immunomodulators, immunostimulants During the past 12 weeks before start
        of treatment and during the study Astemizole Tranquilizers, antidepressants, sedatives,
        hypnotics, antiepileptics and other CNS active agents, except treatment with tricyclics
        that is stable for at least 12 weeks prior to screening and throughout the trial