E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
chronic stable plaque psoriasis |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10071117 |
E.1.2 | Term | Plaque psoriasis |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10050576 |
E.1.2 | Term | Psoriasis vulgaris |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10037153 |
E.1.2 | Term | Psoriasis |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
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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 demonstrate that topical treatment with the generic calcipotriol-betamethasone ointment formulation is therapeutically equivalent to the originator product Daivobet® ointment in the treatment of chronic stable plaque psoriasis as determined by the percentage reduction in modified Psoriasis Area and Severity Index (PASI). |
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E.2.2 | Secondary objectives of the trial |
- to demonstrate that topical treatment with the generic calcipotriol-betamethasone ointment formulation is superior to vehicle (company’s ointment formulation) in the treatment of chronic stable plaque psoriasis as determined by the percentage reduction in modified Psoriasis Area and Severity Index (PASI). - to assess the efficacy of the generic calcipotriolbetamethasone ointment formulation in comparison to the originator product Daivobet® and vehicle (company’s ointment formulation) in the treatment of chronic stable plaque psoriasis in terms of improvement in: o Investigator's Psoriasis Global Assessment (IPGA) score; o Body Surface Area (BSA) affected by psoriasis; o Patient’s Psoriasis Global Assessment (PPGA) score. - to assess the safety and local tolerance of the generic calcipotriol-betamethasone ointment formulation in comparison to the originator product Daivobet® and vehicle (company’s ointment formulation). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
[1] Male or female patients ≥18 years of age. [2] Clinical diagnosis of chronic stable (at least 6 months) plaque psoriasis amenable to topical treatment and involving arms and/or legs and/or trunk (but excluding face, scalp, genitals and intertriginous areas). [3] Psoriasis affecting less than 30% of the body surface area (BSA). [4] A modified PASI score of ≥5 to ≤15 at baseline (Visit 2). [5] Female patients of childbearing potential must have a negative pregnancy test prior to randomisation and must agree to use an appropriate method of contraception during the study. [6] Patients willing and able (e.g. mental and physical condition) to participate in all aspects of the study, including use of medication, completion of subjective evaluations, attending scheduled visits, and compliance with protocol requirements as evidenced by providing signed written informed consent. |
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E.4 | Principal exclusion criteria |
[1] History of hypersensitivity or intolerance to any active substance or any of the excipients of the study medication. [2] Current diagnosis of unstable forms of psoriasis in the area(s) to be treated with study medication, including guttate, erythrodermic, exfoliative, or pustular psoriasis. [3] Other inflammatory skin disease in the area(s) to be treated with study medication that may confound the evaluation of plaque psoriasis (e.g., atopic dermatitis, contact dermatitis, tinea corporis). [4] Presence of pigmentation, extensive scarring, pigmented lesions, or sunburn in the area(s) to be treated with study medication which could interfere with efficacy and safety evaluations. [5] History of psoriasis unresponsive to topical treatments. [6] Presence of any of the following skin conditions in the treatment area: viral infections (e.g. herpes simplex, herpes zoster, varicella), fungal and bacterial skin infections, parasitic infections, skin manifestation in relation to tuberculosis, perioral dermatitis, atrophic skin, striae atrophicae, fragility of sin veins, ichthyosis, acne vulgaris, acne rosacea, dermal ulcers and wounds. [7] Other severe acute or chronic concomitant disease with severe impairment of the general condition. [8] Other concomitant diseases which may - taking the present knowledge into account - influence the parameters evaluated in the study in a way that an objective evaluation would be impossible. [9] Current or past history or signs/symptoms suggestive of a clinically significant abnormality in calcium homeostasis with hypercalcaemia, vitamin D toxicity, severe renal impairment (CRCL <30 ml/min), or severe hepatic disorder (total bilirubin, AST, ALT, GGT, or AP >3 times the upper limit of normal). [10] Use of topical anti-psoriatic therapy (including topical retinoids, topical corticosteroids, vitamin D analogues, salicylic acid, anthralin, coal tar) within 2 weeks prior to baseline (Visit 2) and during the study. [11] Use of systemic corticosteroids (including inhaled and nasal steroids) within 4 weeks prior to baseline (Visit 2) and during the study. [12] Use of other systemic anti-psoriatic therapy, systemic antibiotics, or systemic anti-inflammatory agents within 1 month prior to baseline (Visit 2) and during the study. [13] Use of immunosuppressive drugs (e.g., tacrolimus, pimecrolimus) or oral retinoids (e.g., acitretin) within 2 months prior to baseline (Visit 2) and during the study. [14] Chemotherapy or radiation therapy within 3 months prior to baseline (Visit 2) and during the study. [15] Use of systemic anti-psoriatic biologic therapy (e.g., alefacept, etanercept, infliximab, efalizumab, adalimumab) within 6 months prior to baseline (Visit 2) and during the study. [16] Psoralen + UVA (PUVA) therapy or UVB therapy within 1 month prior to baseline (Visit 2) and during the study. [17] Use of calcium supplements during the study. [18] More than 400 IU/day of vitamin D or vitamin D analogues during the study. [19] Initiation of or changes in non-anti-psoriatic concomitant medication(s) that could affect psoriasis (e.g., beta-blockers, lithium, ACE inhibitors) during the study. [20] Initiation of or changes to concomitant medication that could affect calcium metabolism (e.g., antacids, thiazide and/or loop diuretics, antiepileptics) during the study. [21] Use of tanning booth, sun lamps, or non-prescription UV light sources within 2 weeks prior to baseline (Visit 2) and during the study. [22] Use of topical skin products other than the assigned treatment (including moisturisers, new brands of make-up, creams, ointments, lotions, and powders) during the study. [23] Phototherapy within 2 weeks prior to baseline (Visit 2) and during the study. [24] Women with existing or intended pregnancy or during lactation. [25] Reasonable doubt concerning the co-operation of the patient. [26] Participation in another clinical study within the last 30 days prior to inclusion in this study. [27] Participation in this study at an earlier date. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean percent change from baseline in modified PASI score at the end of week 4. This endpoint undergoes descriptive and comparative statistical Evaluation. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After completion of the clinical part of the trial and database closure and blind review. |
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E.5.2 | Secondary end point(s) |
- Mean percent change from baseline in modified PASI score at the end of week 1. - Proportion of patients with a reduction in modified PASI score of >75% between baseline and end of week 4 (responder). - Proportion of patients with a reduction in modified PASI score of >50% between baseline and end of week 4. - Mean percent change from baseline in IPGA at the end of week 1 and week 4. - Mean percent change from baseline in PPGA at the end of week 1 and week 4. - Proportion of patients with controlled disease (defined as "clear" or "almost clear") in IPGA at the end of week 4. - Proportion of patients with controlled disease (defined as "clear" or "almost clear") in PPGA at the end of week 4. - Mean percent change from baseline in BSA affected by psoriasis at the end of week 1 and week 4. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After completion of the clinical part of the trial and database closure. These endpoints undergo descriptive and comparative statistical Evaluation. |
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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 |
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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 | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 24 |
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 | No |
E.8.7 | Trial has a data monitoring committee | No |
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 | 12 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 12 |