E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Investigative study of pathogenesis/treatment of calcineurin inhibitor vs. corticosteroid confirmatory study to prior study: Pimecrolimus and Epidermal Barrier Function, Protocol No. ELBE-2005, EudraCT No.: 2004-004824-11 |
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MedDRA Classification |
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 confirm that the percentage of physiological lamellar bodies in the epidermis will be higher after three weeks treatment with pimecrolimus cream 1% than after three weeks treatment with triamcinolone acetonid cream 0.1%. |
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E.2.2 | Secondary objectives of the trial |
1. To investigate if 1% pimecrolimus cream leads to a reduction of pathological ultrastructural parameters of AD representing the permeability barrier of the skin after three weeks of treatment in lesional AD epidermis compared to standard steroid therapy (0.1% triamcinolone acetonide). 2. To explore the epidermal effect on proliferation rate (Ki-67 assay), differentiation (cytokeratins, involucrin, loricrin, filaggrin, and antimicrobial peptides), and stratum corneum lipid content (sebu-tape analysis) of 1% pimecrolimus cream compared to 0.1% triamcinolone acetonide cream treatment. 3. To explore the effect of 1% pimecrolimus cream induced changes in hydration and transepidermal water loss of the epidermis compared to a standard steroid (0.1% triamcinolone acetonide cream) treatment. 4. Blood samples will be screened for filaggrin mutations and results correlated with structural changes.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects may be included only if the following apply at the baseline visit (day 0, before first application of study medication). Patients to be included are: · Males and females of any race. · >= 18 years old. · Have atopic dermatitis as defined by Hanifin and Rajka criteria. · History of mild to moderate atopic dermatitis · At least 10 % of each upper limb affected by atopic dermatitis excluding the surface area of the hands, as these will not be treated in order to avoid cross-contamination. As reference: one hand (palm and fingers) corresponds to 10% of patient’s upper limb surface. · One specific, representative area of the disease on each upper limb with similar size and severity on both upper limbs. These will be considered the target lesions. · A target lesion score of at least 3 to 8 (on a scale of 0-12) for both right and left target lesions and not differing more than 1 score point between the right and left sides. · Must be able to suspended treatment of atopic dermatitis with other therapies for the duration of the study (3-5 weeks). · Must be informed of study procedures and have signed the informed consent form approved for the study.
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E.4 | Principal exclusion criteria |
Females: Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG test. Females of childbearing potential and not practicing a medically approved method of contraception during and up to at least 4 weeks after the end of treatment. ‘Medically approved’ contraception may include implants, injectables, combined oral contraceptives, IUDs, but also abstinence at the discretion of the investigator. Other therapies/medications: · Prior phototherapy or systemic therapy known to or suspected to have an effect on atopic dermatitis within 14 days prior to first application of study medication. Patients on a low stable dose of inhaled steroids (dose known to have negligible systemic absorption) and systemic antihistamines may participate. · Topical therapy known to or suspected to have an effect on atopic dermatitis (including topical steroids, topical tacrolimus ointment or topical pimecrolimus cream) on the upper limbs within 7 days prior to first application of study medication. · Topical therapy known to or suspected to have an effect on atopic dermatitis on other areas than upper limbs if total body surface treated is higher than 20% (due to the higher risk of systemic absorption affecting the lesions of the upper limbs) within 7 days prior to first application of study medication Concurrent diseases / conditions and history of their diseases / conditions: · Patients who have signs of skin atrophy and corticoid damage on the target areas · Patients who are immunocompromised (e.g. lymphoma, AIDS, Wiskott-Aldrich Syndrome) · Patients who have concurrent skin disease (e.g. impetigo) on or near the study area which could interfere with study evaluations · Patients who have acute viral skin infections (e.g. herpes simplex, varicella zoster) Investigational drug / therapy use. · Patients who have used investigational drugs within 8 weeks prior to first application of study medication or intend to use other investigational drugs during the course of the study Ingredient hypersensitivity · Patients with known hypersensitivity to any ingredient of the study medication (see technical information sheet) Compliance / reliability / investigator judgment · Patients who are, in the opinion of the investigator, known to be unreliable or non-compliant with medical treatment, or are known to miss appointments (according to patient records) · Patients who have drug abuse problems, mental dysfunction or other factors limiting their ability to cooperate fully · Patients who have any other condition or prior/present treatment which, in the opinion of the investigator, will render the patient ineligible for the study
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E.5 End points |
E.5.1 | Primary end point(s) |
The normalization of physiological lamellar bodies after three weeks of treatment with pimecrolimus cream to be determined through ultrastructual analysis will be the primary endpoint of the study. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
ultrastructural changes in the epidermis |
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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 | Yes |
E.7.1.3.1 | Other trial type description |
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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 | No |
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 | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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 | Yes |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | 22 |