| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| not applicable |
| PAZIENTEI EMICRANICI |
|
| 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 | 14.1 |
| 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 |
| To evaluate of efficacy of rizatriptan 10 mg lyophilized wafer (MLT) compared to placebo in the treatment of acute migraine in patients with unilateral autonimic symptoms (UAs: unilaterl lacrimation, eye redness, eyelid oedema, nasal congestion or rhinorrehoea, miosis or ptosis, forehead or facial sweating) during the attack. |
| Valutare efficacia di Rizatriptan 10 mg liofilizzato orale (RPD)rispetto al placebo nel trattamento acuto dell'emicrania in pazienti con sintomi trigemico-autonomici unilaterale(UAs:lacrimazione iperenia congiuntvale, edema palpebrale, congestione nasale, rinorrea, miosi, ptosi, sudorazione facciale o frontale unilaterali), durante l'attacco. |
|
| E.2.2 | Secondary objectives of the trial |
| a. The rizatriptan treatment group is superior to placebo, as measured by the percentage of patients who have pain freedom at 2 hours postdose. b. The rizatriptan treatment group is superior to placebo, as measured by the percentage of patients who have pain relief at 2 hours postdose. c. The rizatriptan treatment group is superior to placebo, as measured by the percentage of patients free of nausea at 2 hours. a. The rizatriptan treatment group is superior to placebo, as measured by the percentage of patients free of photophobia at 2 hours. b. The rizatriptan treatment group is superior to placebo, as measured by the percentage of patients free of phonophobia at 2 hours. c. The rizatriptan treatment group is superior to placebo, as measured by the percentage of patients who have sustained pain freedom 2–24 hours postdose. d. The rizatriptan treatment group is superior to placebo, as measured by the percentage of patients who have sustained pain relief 2–24 hours postdose. |
| Il GdTr con rizatriptan e' sup al PL sulla base della % di paz che ha pain free dopo 2h dall’assunzione del farm.Il GdTr con rizatriptan e' sup al PL sulla base della % di paz che ha - 50% del pain relief dopo 2h dall’assunzione del farmaco.Il GdTr con rizatriptan e' sup al PL sulla base della % di paz che presenta scomparsa della nausea dopo 2h dall’assunzione del farmaco.Il GdTr con rizatriptan e' sup al PL sulla base della % di paz che presenta scomparsa della fotofobia dopo 2h dall’assunzione del farmaco.Il GdTr con rizatriptan e' sup al PL sulla base della % di paz che presenta scomparsa della fonofobia dopo 2h dall’assunzione del farmaco.Il GdTr con rizatriptan e' sup al PL sulla base della % di paz che ha pain free dopo 2 ore persistente nelle 24h dopo l’assunzione del farm.Il GdTr con rizatriptan e' sup al PL sulla base della % di paz che ha - 50% del pain relief dopo 2h persistente nelle 24h(sustained pain relief) dopo l’assunzione del farm |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| A patient will be eligible to participate in this study if all of the following criteria apply: a. Patient is ≥18 years of age at screening. b. Patient has had a history of migraine with or without aura > 1 year with ≥1 and ≤8 moderate or severe migraine attacks per month in the 2 months prior to screening that typically last longer than 2 hours13. c. During the migraine attack (if untreated) patient has every time at least 1 of the following symptoms due to the activation of the trigeminal-autonomic reflex (UAs): unilateral conjunctival injection and/or lacrimation and/or nasal congestion/rhinorrhea and/or ptosis and/or eyelid oedema and/or forehead/facial sweating d. A patient who is of reproductive potential agrees to remain abstinent or use (or have their partner use) 2 acceptable methods of birth control within the projected duration of the study (intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge, condoms, vasectomy) e. Patient is: (a) male or (b) female and not of reproductive potential is eligible without requiring the use of contraception. f. Patient is judged to be in satisfactory health in the opinion of the investigator based on screening assessment including medical history, physical examination, and laboratory testing carried out within ~2 months prior to study treatment. g. Patient understands the study procedures and voluntarily agrees to participate by giving written informed consent. h. Patient is able to complete the study questionnaire(s) and paper diary. |
| 1.4.1 Criteri di Inclusione Dovranno essere rispettati tutti i seguenti criteri di inclusione: a. Eta' ≥18 anni. b. Storia di emicrania senza aura o con aura da almeno 1 anno con frequenza di attacchi compresa tra 1 e 8 al mese nei 2 mesi precedenti13. c. Nei pazienti di sesso femmninile in eta' riproduttiva, per tutta la durata dello studio, e' richiesta la astinenza sessuale o l’uso personale o da parte del partner di metodi accettati di controllo delle nascite (contraccettivi orali, IUD, diaframma con spermicida, profilattico, vasectomia) d. Buone condizioni generali di salute, secondo il giudizio dell’investigatore, sulla base di anamnesi, esame obiettivo ed esami di laboratorio eseguiti nel corso dei 2 mesi precedenti lo studio e. Capacita' di comprendere il protocollo di studio e adesione volontaria mediante sottoscrizione di consenso informato. f. Capacita' di compilare il questionario e la carta diario |
|
| E.4 | Principal exclusion criteria |
| A patient will not be eligible to participate in this study if any of the following criteria apply: a. Patient is pregnant or breast-feeding, or expecting to conceive within the projected duration of the study. b. Patient has difficulty distinguishing his/her migraine attacks from tension or interval headaches. c. Patient has a history of predominantly mild migraine attacks or migraines usually resolved spontaneously in less than 2 hours. d. Patient has basilar or hemiplegic migraine headache. e. Patient has more than 15 headache-days per month or has taken medication for acute headache on more than 10 days per month in any of the 3 months prior to screening. f. Patient is taking migraine Propranolol or has discontinued it from less than 14 days g. Patient is taking migraine prophylactic medication where the prescribed daily dose has changed during the 3 months prior to screening. h. Patient was > 50 years old at age of migraine onset. i. Patient has a recent history (within the past 5 years) or current evidence of drug or alcohol abuse or is a “recreational user” of illicit drugs. j. Patient has a concomitant use of propranolol, ergot derivatives, methysergide or MAO inhibitors k. Patient has a demonstrated hypersensitivity to any marketed 5HT1B/1D receptor agonist. l. Patient has a history or clinical evidence of ischemic heart disease (e.g., angina pectoris of any type, history of myocardial infarction or documented silent ischemia) or symptoms or findings consistent with ischemic heart disease, coronary artery vasospasm (including Prinzmetal’s variant angina), or other significant underlying cardiovascular disease. m. Patient has clinical, laboratory, or ECG evidence of uncontrolled hypertension, uncontrolled diabetes, or significant pulmonary, renal, hepatic, endocrine, or other systemic disease in the opinion of the investigator. n. Patient has, in the opinion of the investigator, other confounding pain syndromes, psychiatric conditions such as uncontrolled major depression based on criteria such as DSM-IV, dementia or significant neurological disorders other than migraine. o. Patient has a history of neoplastic disease ≤ 5 years prior to signing informed consent. p. Patient has a history of gastric or small intestinal surgery (including gastric bypass surgery or banding), or has a disease that causes malabsorption. q. Patient has a history or current evidence of any clinically significant disease that according to the investigator might confound the results of the study, complicate the interpretation of the study results, interfere with the patient’s participation for the full duration of the study, or pose an additional undue risk to the patient. |
| Il paziente non sara' arruolabile nello studio qualora si verifichi almeno uno dei seguenti criteri: a. Gravidanza, allattamento o previsione di concepimento nel corso dello studio b. Incapacita' a distinguere gli attacchi emicranici da episodi di cefalea di tipo tensivo c. Emicrania caratterizzata da attacchi di lieve intensita' o che possano risolversi spontaneamente entro 2 ore d. Emicrania emiplegica o basilare. e. Presenza di piu' di 15 giorni di cefalea al mese o assunzione di farmaci per l’attacco per piu' di 10 giorni al mese in alcuno dei 3 mesi precedenti lo screening. f. Assunzione di propranololo in atto o nel corso degli ultimi 14 giorni g. In caso di assunzione concomitante di terapia profilattica dell’emicrania, quando la dose giornaliera sia variata nel corso dei 3 mesi precedenti lo screening h. Emicrania esordita in eta' superiore ai 50 anni. i. Storia recente (< 5 anni) o attuale di abuso di farmaci, alcool o sostanze psicotrope illecite j. Uso di ergotaminici, metisergide o inibitori delle MAO. k. Dimostrata ipersensitivita' ad alcuno dei farmaci agonisti recettoriali 5HT1B/1D in commercio. l. Anamnesi positiva o evidenza clinica di cardiopatia ischemica (es: angina pectoris di qualunque tipo, infarto miocardico o ischemia miocardica silente) o sintomi o elementi comprovanti cardiopatia ischemica, vasospasmo coronario (incluso la angina di Prinzmetal) o altre significative sottostanti patologie cardiovascolari m. Evidenza clinica, laboratoristica e ECGrafica di ipertensione arteriosa non controllata, diabete non controllato, o patologie respiratorie, renali, epatiche, endocrine o di altro tipo, significative secondo il giudizio dell’investigatore n. Concomitanza, secondo il giudizio dell’investigatore, di altre patologie dolorose confondenti, patologie psichiatriche quali depressione maggiore non controllata, demenza od altre patologie neurologiche di rilievo. o. Anamnesi positiva per malattia neoplastica nei 5 anni precedenti p. Anamnesi positive per intervento chirurgico a carico di stomaco o intestine tenue (incluso intervento per by-pass o bendaggio gastrico) o altra patologia possibile causa di malassorbimento. q. Anamnesi positiva o evidenza clinica di qualsiasi forma patologica che secondo l’investigatore possa compromettere i risultati dello studio, complicare la loro interpretazione, interferire con la partecipazione del paziente durante tutta la durata dello studio o causargli un indebito rischio aggiuntivo. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Primary Measure: a. Rating of headache severity at baseline and 2 hours postdose. Headache severity will be measured on the following verbal scale: 0 = no pain; 1 = mild pain; 2 = moderate pain; 3 = severe pain. Timing of all efficacy measurements is relative to the first dose of study medication. Secondary and Exploratory Measures: a. Rating of headache severity at 0.5, 1, 1.5, 2, 3, 4, and 24 hours post dose. b. Presence or absence of associated symptoms (nausea, vomiting, photophobia, or phonophobia) at the same time points as headache severity ratings. c. Rating of functional disability at the same time points as headache severity ratings. d. Presence or absence of moderate/severe headache recurrence within 48 hours. e. Presence or absence of return to mild/moderate/severe headache (for patients who were pain-free at 2 hours) within 48 hours. f. Use of rescue medication. |
| Primarie: a. Intensita' della cefalea al baseline e dopo 2 ore dall’assunzione del farmaco in studio. L’intensita' verra' misurata sulla base della seguente scala: 0 = assenza di dolore; 1 = dolore lieve; 2 = dolore moderato; 3 = dolore severo. Il timing di tutte le misure di efficacia verra' riferito al momento di assunzione del farmaco. Secondarie: a. Intensita' della cefalea dopo 0.5, 1, 1.5, 2, 3, 4, e 24 ore dall’assunzione del farmaco in studio. b. Presenza o assenza di sintomi associati (nausea, vomito, fotofobia, o fonofobia) ai medesimi intervalli di tempo predefiniti c. Disabilita' funzionale ai medesimi intervalli di tempo predefiniti. d. Presenza o assenza di recidiva di cefalea moderata o severa entro le successive 48 ore. e. Presenza o assenza di recidiva di cefalea lieve/moderata/severa entro le successive 48 ore (limitatamente ad i pazienti pain free dopo 2 ore) f. Ricorso a farmaci di emergenza. |
|
| 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 | No |
| 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) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| 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
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| 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 | 12 |
| E.8.9.1 | In the Member State concerned days | 0 |
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