E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10023686 |
E.1.2 | Term | Lamellar ichthyosis |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate the efficacy of oral liarozole, given at a dose of 75 mg o.d. or 150 mg o.d. vs. placebo in subjects with lamellar ichthyosis, as measered by the Investigator's Global Assessment at the end of 12 weeks of treatment. |
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E.2.2 | Secondary objectives of the trial |
· Investigator’s Global Assessment at 8 weeks of treatment · Overall Scaling Score · Individual severity scores for erythema and pruritus · Quality of Life (QOL): generic (SF-36) and disease specific (DLQI) questionnaires · Use of emollients and mechanical scale removal · Safety and tolerability · Pharmacokinetics · Photographs |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects of either sex aged 18 years or older
2. Clinical diagnosis of lamellar ichthyosis with at visits 1 and 2 an Investigator’s Global Assessment of at least 3 when defined as follows: Investigator’s global assessment of the overall severity of subject’s lamellar ichthyosis at a particular time point, taking into consideration the two individual characteristics of ichthyosis (scaling and/or erythema), measured by the following 5-point Likert scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe).
3. Women of childbearing potential are asked to use simultaneously 2 forms of effective contraception during the trial. The first one must be a hormonal contraceptive containing an association of progestin and estrogen and must be taken for at least 1 month (full cycle) before the start of treatment (visit 2). The second one must be a barier method with spermicide and must be used at least from visit 1. Both forms must then be used during treatment and until one month after the end of the treatment period.
4. Women of childbearing potential should have a negative pregnancy test at screening visit (Visit 1), confirmed by another pregnancy test at Visit 2 before randomization.
5. Subjects wearing contact lenses must agree not to wear their lenses and to use glasses when necessary for the entire treatment period.
6. Subjects are, except for their lamellar ichthyosis, in good general health and free of any disease state or physical condition that, in the investigator’s opinion, might impair evaluation of their lamellar ichthyosis.
7. Subjects signed informed consent. |
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E.4 | Principal exclusion criteria |
1. Concurrent inflammatory skin disease unrelated to ichthyosis.
2. Subject is receiving topical (except emollient) or UV treatment for ichthyosis in the 2 weeks prior to the start of treatment (Visit 2).
3. Subject is receiving systemic therapy for ichthyosis in the 4 weeks prior to the start of treatment (Visit 2).
4. Subject is pregnant or breast feeding.
5. History or suspicion of alcohol or drug abuse.
6. Significant co-existing hepatic, renal, immune disease, chronic pancreatitis, osteoporosis or a history indicating adrenal cortex dysfunction.
7. Heart disorder requiring treatment, or a myocardial infarction within the previous 24 weeks or a history of heart-failure or clinically relevant cardiac arrhythmia.
8. Clinically significant abnormal electrocardiogram-intervals or morphology of the electrocardiogram; QT or QTc >470 ms in women or >450 ms in men.
9. Subjects with risk factors for a QT/QTc prolongation (cardiac insufficiency, hypokalemia, a family history of long QT syndrome).
10. History of hypersensitivity to retinoids.
11. History of hypersensitivity to any of the ingredients in the trial medication.
12. Clinically relevant laboratory abnormalities at screening, especially levels of blood triglycerides, cholesterol and liver function parameters.
13. Use of Vitamin A supplements in the 4 weeks prior to the start of treatment or during the trial.
14. Use of disallowed drugs, mainly drugs metabolized by the CYP450 system during the treatment period.
15. Use of immune-suppressive drugs including topical or systemic corticosteroids.
16. Participation in an investigational trial 30 days prior to the start of the trial (Visit 1). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the percentage of responders to treatment. A subject is considered a responder if the Investigator's Global Assessment is decreased with at least 2 points on the 5-point Likert scale by the end of the treatment period. |
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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 | Yes |
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) | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |