E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic stable plaque psoriasis. |
Przewlekła stabilna łuszczyca plackowata |
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E.1.1.1 | Medical condition in easily understood language |
Chronic stable plaque psoriasis. |
Przewlekła stabilna łuszczyca plackowata |
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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 | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10071117 |
E.1.2 | Term | Plaque psoriasis |
E.1.2 | System Organ Class | 100000004858 |
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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). |
Wykazanie na podstawie zmodyfikowanego Wskaźnika Nasilenia Zmian Łuszczycowych (wskaźnik PASI), że miejscowe leczenie stabilnej łuszczycy plackowatej maścią zawierającą kalcitopriol-betametazon jest terapeutycznie równoważne z leczeniem oryginalnym produktem- maścią Daivobet® |
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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 calcipotriol-betamethasone 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: - Investigator's Psoriasis Global Assessment (IPGA) score; - Body Surface Area (BSA) affected by psoriasis; - 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). |
- Wykazanie na podstawie zmniejszenia nasilenia łuszczycy wg wskaźnika PASI, że miejscowe leczenie przewlekłej łuszczycy plackowatej lekiem badanym w postaci maści zawierającej kalcipotriol-betametazon jest skuteczniejsze niż leczenie podłożem maściowym (Lek Pharmaceuticals d.d) - ocena skuteczność leku badanego w postaci maści zawierającej kalcipotriol-betametazon w porównaniu z oryginalnym lekiem Daivobet® oraz podłożem maściowym (Lek Pharmaceuticals d.d) w leczeniu pacjentów z przewlekłą stabilną łuszczycą plackowatą biorąc pod uwagę poprawę stanu zdrowia pacjentów w oparciu o następujące kryteria: całościowa lekarska ocena objawów łuszczycy (IPGA) powierzchnia zmian łuszczycowych (BSA) całościowa ocena pacjenta zmian łuszczycowych (PPGA) - Ocena bezpieczeństwa i lokalnej tolerancji leku badanego w postaci maści zawierającej kalcipotriol-betametazon w porównaniu z oryginalnym lekiem Daivobet® oraz podłożem maściowym (Lek Pharmaceuticals d.d)
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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. [7] An albumin-corrected serum calcium level below the upper reference range limit. |
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E.4 | Principal exclusion criteria |
- History of hypersensitivity or intolerance to any active substance or any of the excipients of the study medication - History of hypersensitivity to Adrenocorticotropic hormone (ACTH), Synacthen® or Synacthen® Depot - Current diagnosis of unstable forms of psoriasis in the area(s) to be treated with study medication, including guttate, erythrodermic, exfoliative, or pustular psoriasis - Other inflammatory skin disease in the area(s) to be treated with study medication that may confound the evaluation of plaque psoriasis - Presence of pigmentation, extensive scarring, pigmented lesions, or sunburn in the area(s) to be treated with study medication which could interfere with efficacy evaluation - History of psoriasis unresponsive to topical treatments - Viral lesions of the skin - Fungal or bacterial skin infections - Parasitic infections - Skin manifestations in relation to tuberculosis or syphilis - Perioral dermatitis - Atrophic skin, striae atrophicae - Fragility of skin veins - Ichthyosis - Acne vulgaris, acne rosacea, rosacea - Dermal ulcers, wounds - Perianal and genital pruritus - Allergic disorders or susceptibility for allergic reactions - Active infectious diseases - Peptic ulcer - Refractory heart failure - Any of the following conditions, whether known or suspected: endocrine disorders, Cushing’s syndrome, primary adrenocortical insufficiency, diabetes mellitus - 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) - Use of topical anti-psoriatic therapy within 2 weeks prior to baseline (Visit 2) and during the study - Use of systemic corticosteroids within 3 months prior to baseline (Visit 2) and during the study - 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 - Use of immunosuppressive drugs or oral retinoids within 2 months prior to baseline (Visit 2) and during the study - Chemotherapy or radiation therapy within 3 months prior to baseline (Visit 2) and during the study - Use of systemic anti-psoriatic biologic therapy within 6 months prior to baseline (Visit 2) and during the study - Psoralen + UVA (PUVA) therapy or UVB therapy within 1 month prior to baseline (Visit 2) and during the study - Use of calcium supplements during the study - More than 400 IU/day of vitamin D or vitamin D analogues during the study - Initiation of or changes in non-anti-psoriatic concomitant medication(s) that could affect psoriasis during the study - Initiation of or changes to concomitant medication that could affect calcium metabolism during the study - Change in sleep pattern within 1 month prior to baseline (Visit 2) and during the study - Initiation of or changes in oestrogen therapy (including contraceptives), antidepressant medications and any other medication known to affect cortisol levels or HPA axis integrity within 1 month prior to baseline (Visit 2) and during the study - Use of CYP P450 3A4 inducers within 1 month prior to baseline (Visit 2) and during the study - Use of systemic CYP P450 3A4 inhibitors (e.g. ketoconazole, itraconazole, metronidazole) within 1 month prior to baseline (Visit 2) and during the study - Use of topical CYP P450 3A4 inhibitors (e.g. ketoconazole) within 2 weeks prior to baseline (Visit 2) and during the study - Use of tanning booth, sun lamps, or non-prescription UV light sources within 2 weeks prior to baseline (Visit 2) and during the study - 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 - Phototherapy within 2 weeks prior to baseline (Visit 2) and during the study - Pregnancy or breast-feeding - Women of childbearing potential unable or unwilling to undergo pregnancy tests and practice adequate contraceptive measures. Reliable methods for women are hormonal contraceptives, surgical intervention (e.g. tubal ligation), intrauterine device (IUD) and sexual abstinence - Any other condition of the patient (e.g., serious or unstable medical or psychological condition, acute psychosis) that in the opinion of the investigator may compromise evaluation of the study treatment or may jeopardize patient’s safety, compliance or adherence to protocol requirements - Previous enrolment in this study or participation in any other drug investigational trial within the past 3 months prior to enrolment - Alcohol /drug dependence or abuse (excluding tobacco abuse) - Legal incapacity and/or other circumstances rendering the patient unable to understand the nature, scope and possible consequences of the study - Unreliability or lack of cooperation |
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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. |
Średnia procentowa zmiana w skali PASI od punktu wyjściowego do końca tygodnia 4. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After week 4 of the treatment. |
po 4 tygodniach leczenia |
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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 and week 2. - 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, week 2, and week 4. - Mean percent change from baseline in PPGA at the end of week 1, week 2, 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 measurement at the end of week 1, week 2, and week 4. |
• Średnia procentowa zmiana od wartości wyjściowej w zmodyfikowanej skali PASI między tygodniem 1 a tygodniem 2 • Odsetek pacjentów z redukcją wyniku zmodyfikowanej skali PASI >75% między punktem wyjściowym a końcem tygodnia4 (odpowiedź) • Odsetek pacjentów z redukcją wyniku zmodyfikowanej skali PASI >50% między punktem wyjściowym a końcem tygodnia 4 • Średnia procentowa zmiana w ocenie skali IPGA od wartości wyjściowej na koniec tygodnia 1, tygodnia 2 i tygodnia 4. • Średnia procentowa zmiana w ocenie skali PPGA od wartości wyjściowej na koniec tygodnia 1, tygodnia 2 i tygodnia 4 • Odsetek pacjentów z chorobą kontrolowaną określony na podstawie oceny IPGA na koniec tygodnia 4. • Odsetek pacjentów z chorobą kontrolowaną określony na podstawie oceny PPGA na koniec tygodnia 4. • Średnia procentowa zmiana od wartości wyjściowej w pomiarze BSA na koniec tygodnia 1, tygodnia 2, tygodnia 4.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After completion of study and closure of data base. |
po zakończeniu badania i zamknięciu bazy danych |
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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 | No |
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 | No |
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 | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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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LVLS |
Ostatnia wizyta ostatniego pacjenta |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |