| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Epilepsy or other diseases in which using: carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, topiramate and valproate in mono or politerapy |
| Epilessia o altra condizione patologica in cui sia indicato l'utilizzo di: carbamazepina, lamotrigina, levetiracetam, oxcarbazepina, topiramato e valproato in mono o politerapia |
|
| E.1.1.1 | Medical condition in easily understood language |
| Epilepsy or other diseases in which using: carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, topiramate and valproate alone or in combination |
| Epilessia o altra malattia in cui sia indicato l'utilizzo di: carbamazepina, lamotrigina, levetiracetam, oxcarbazepina, topiramato e valproato da soli o in associazione |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 15.0 |
| E.1.2 | Level | SOC |
| E.1.2 | Classification code | 10037175 |
| E.1.2 | Term | Psychiatric disorders |
| E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 15.0 |
| E.1.2 | Level | SOC |
| E.1.2 | Classification code | 10029205 |
| E.1.2 | Term | Nervous system disorders |
| E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
| 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 |
| The primary objective is to provide high-quality evidence on potential risks associated with substitution of the currently taken AED product (carbamazepine,valproic acid, topiramate, oxcarbazepine, levetiracetam or lamotrigine) with an equivalent product, using as endpoint changes in serum drug levels at steady-state after substitution compared with baseline. |
| L'obiettivo primario dello studio è di ottenere evidenze di elevata qualità sulle conseguenze associate alla sostituzione del FAE originariamente assunto (carbamazepina, lamotrigina, levetiracetam, oxcarbazepina, topiramato e valproato) con un prodotto equivalente, utilizzando come endpoint primario le variazioni dei livelli sierici del principio attivo in esame rispetto al basale. |
|
| E.2.2 | Secondary objectives of the trial |
| Secondary objectives will be the assessment of inter-subject variability in serum drug concentration on an unchanged treatment schedule, and evaluation of potential short-term changes in seizure control and adverse events rate. |
| Obiettivi secondari saranno:(i) la valutazione del rischio comparativo di eventi avversi in seguito alla sostituzione rispetto alla non sostituzione; (ii) la valutazione della variabilità intraindividuale dei livelli sierici dei FAE in soggetti che continuano la terapia con il prodotto originariamente prescritto. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| The study will be conducted in adults of either gender fulfilling the following inclusion criteria: (i) 18 years of age or older; (ii) currently being treated and at steady-state with any product (brand or generic) of carbamazepine, valproic acid, topiramate, oxcarbazepine, levetiracetam and/or lamotrigine administered in two or three divided daily doses, either alone or in combination with other drugs; (iii) a diagnosis of epilepsy or any other condition justifying prescription of AED therapy; (iv) being admitted to hospital for observation/diagnostic evaluation; (v) expected to remain on the currently prescribed drug treatment for at least 5 days (or 6 days for patients receiving lamotrigine or topiramate without enzyme inducers, or receiving lamotrigine combined with enzyme inducers plus valproate) following admission to hospital; (vi) willingness to provide free, informed consent. |
| Lo studio sarà condotto in adulti di ambo i generi, in base ai seguenti criteri di inclusione: (i) età pari o superiore a 18 anni; (ii) trattamento allo steady steady con qualunque prodotto (originatore o generico) di carbamazepina (CBZ), lamotrigina (LTG), levetiracetam (LEV), oxcarbazepina (OXC), topiramato (TPM) o valproato (VPA), in mono o politerapia, per epilessia o altre indicazioni; (iii) necessità di ricovero ospedaliero per osservazione/rivalutazione diagnostica; (iv) presumibile mantenimento della terapia attualmente assunta per almeno 6 giorni dalla data del ricovero; (v) disponibilità a fornire consenso informato. |
|
| E.4 | Principal exclusion criteria |
| Exclusion criteria will be (i) a history of known or suspected poor compliance; (ii) recent changes in drug treatment, including potentially interacting comedication, which may have prevented attainment of steady-state conditions of the AED(s) being tested; (iii) known disorders of gastric motility; (iv) pregnancy or lactation; (v) any condition which is expected to alter the pharmacokinetics of the study drug(s) over the subsequent 5/6 days; (vi) inability to fully understand the nature and implications of the study. Subjects will be free to withdraw from the study at any time, or whenever the investigator considers their participation detrimental to their health. |
| Saranno considerati criteri di esclusione: (1) reperto anamnestico di scarsa compliance; (2) recenti modifiche del trattamento farmacologico, tra cui assunzione di farmaci che potrebbero interagire con i farmaci antiepilettici in studio; (3) alterata motilità gastrica; (4) gravidanza e allattamento; (5) ogni condizione che potrebbe alterare la farmacocinetica dei farmaci sperimentali nei 5-6 giorni successivi all’inizio della sperimentazione; (6) incapacità a comprendere la natura e le implicazioni dello studio. I soggetti saranno liberi di ritirare il proprio consenso in qualunque momento, o qualora lo sperimentatore ritenesse la partecipazione allo studio pericolosa per la loro salute. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Proportion of patients who post-randomization show a greater than 25% change in serum drug concentration compared with baseline |
| Percentuale di pazienti in ciascuno dei due gruppi con una variazione superiore al 25% (post-randomizzazione rispetto al basale) della concentrazione sierica del FAE in esame |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
| (i) Proportion of patients who post-randomization will show a greater than 15% change in mean serum drug concentration compared with baseline; (ii) proportion of patients who post-randomization will show a greater than 50% change in mean serum drug concentration compared with baseline; (iii) proportion of patients who will show a greater than 15, 25% and 50% change in either post-absorptive or trough serum drug concentration compared with baseline; (iv) distribution in individual serum drug concentrations post-randomization compared with baseline (v) mean percent change (and %CV) in serum drug concentration post-randomization compared with baseline; (vi) proportion of patients with adverse events; (vii) adverse event (AEP) scores; (viii) interval elapsed between randomization and the first seizure; (ix) the above outcome measures, by type of AED, specific product utilized, and type of switch (brand to generic and generic to generic). |
| (i) Percentuale di pazienti in ciascuno dei due gruppi con variazione superiore al 15% (post-randomizzazione rispetto al basale) della concentrazione sierica del FAE in esame; (ii ) percentuale di pazienti in ciascuno dei due gruppi con variazione superiore al 50% (post-randomizzazione rispetto al basale) della concentrazione sierica del FAE in esame); (iii) percentuale di pazienti in ciascuno dei due gruppi con variazione superiore al 15%, 25% e 50% (post-randomizzazione rispetto al basale) della concentrazione sierica al picco e alla valle del FAE in esame; (iv) distribuzione nelle concentrazioni sieriche individuali post-randomizzazione rispetto al basale; (v) variazione percentuale media (e CV) della concentrazione sierica post-randomizzazione rispetto al basale in ciascun gruppo; (vi) percentuale di pazienti con effetti avversi nei due gruppi; (vii) scores AEP nei due gruppi; (viii) intervallo decorrente tra la randomizzazione e la prima crisi epilettica; (ix) i parametri precedenti, suddivisi per sottogruppi in base al tipo di FAE, al prodotto utilizzato e al tipo di modifica (da originatore a generico e da generico a generico) . |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| 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 | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Stesso farmaco originatore o generico |
| Same drug brand or generic |
|
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| 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 | 20 |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 36 |
| E.8.9.1 | In the Member State concerned days | 0 |
Print
