E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of stereotypical prolonged seizure |
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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] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10076333 |
E.1.2 | Term | Prolonged seizure |
E.1.2 | System Organ Class | 100000004852 |
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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 |
Evaluation of the long-term safety and tolerability of Staccato alprazolam |
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E.2.2 | Secondary objectives of the trial |
- Evaluation of the probability of success of repeated treatment with Staccato alprazolam (for seizures occurring within the first 12 months [up to a maximum of 10 treated seizures]) - Evaluation of the probability of success of repeated treatment with Staccato alprazolam with no recurrence of seizure(s) up to 2 hours (for seizures occurring within the first 12 months [up to a maximum of 10 treated seizures]) - Evaluation of the long-term pulmonary safety of Staccato alprazolam |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Participant must be ≥12 years of age at the time of signing informed consent (or giving assent, where required) - Participant must have a study caregiver ≥18 years of age at the time of signing the informed consent; the study caregiver(s) must be able to recognize and observe the participant - Participants with an established diagnosis of focal or generalized epilepsy or combined focal and generalized epilepsy with a documented history of stereotypical episodes of prolonged seizures that includes at least 1 of the following: a) Generalized seizure episodes starting with a flurry of absence seizures or myoclonic seizures with a minimum total duration of 5 minutes b) Episodes of a focal seizure with a minimum duration of 3 minutes c) Episodes of a focal seizure or a flurry of myoclonic seizures for at least 90 seconds followed by a generalized/bilateral tonic-clonic seizure with a minimum total duration of 3 minutes - Prior to the Screening Visit, participant completed a study using Staccato alprazolam Additional inclusion criteria for treatment arms 2 to 5: Prior to the Screening Visit, the participant completed the Phase 3 efficacy study with Staccato alprazolam (EP0162) at a clinical site located in the EU, UK, and UA, and experienced an IMP-treated seizure during the Outpatient Treatment Period. |
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E.4 | Principal exclusion criteria |
- Participant has a current history of alcohol or drug use disorder, as defined in the Diagnostic and Statistical Manual of Mental Disorders 5, within the previous 1 year - Participant has a known hypersensitivity to any components of the investigational medicinal product (IMP) or comparable drugs (and/or an investigational device) as stated in this protocol or to albuterol (or similar bronchospasm rescue medication if needed to meet country- specific requirements) - Participant has a history of convulsive status epilepticus in the 8 weeks prior to the Screening Visit - Participant has a history or presence of known nonepileptic seizures which cannot be distinguished from qualifying epileptic seizures - Participant has a clinically significant known airway hypersensitivity (eg, bronchospasm to known allergens, such as pollen, animals, or food) and/or acute respiratory signs/symptoms (eg, shortness of breath, wheezing on lung auscultation) - Participant has a clinically significant chronic pulmonary disorder (eg, asthma, chronic obstructive pulmonary disease, restrictive lung diseases [including idiopathic pulmonary fibrosis]) and/or recent history or presence of hemoptysis or pneumothorax - Participant has ever been diagnosed with asthma (irrespective of current treatment) - Participant has had a positive antigen test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and experienced moderate to severe signs/symptoms of respiratory distress necessitating hospitalization or outpatient treatment such as ambulatory oxygen, extensive treatment with inhaler medications, and/or oral medications for a duration of 4 weeks or more, unless full resolution occurred at least 6 months prior to Screening - Participant has experienced a severe upper respiratory tract infection within 4 weeks or severe bronchitis/pneumonia within 3 months before the Screening Visit - Participant has a history or presence of acute narrow-angle glaucoma - Participant has a condition for which oral alprazolam is contraindicated (eg, myasthenia gravis, severe respiratory insufficiency, and sleep apnea syndrome) - Participant is taking any drug that is a strong CYP3A4 inhibitor, including azole antifungal agents (ketoconazole and itraconazole) and nefazodone - Participant is taking any opioids (eg, fentanyl, oxycodone, morphine) or sedative hypnotics on a chronic basis - Participant is taking nonselective beta blockers (eg, propranolol, nadolol, and timolol) on a chronic basis - Participant has an FEV1 <80 % of predicted forced expiratory volume in 1 second (FEV1) as measured via spirometry at the Screening Visit |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Frequency of treatment-emergent adverse events (TEAEs) 2. Frequency of TEAEs leading to withdrawal from study 3. Frequency of serious TEAEs |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1&3: From Baseline up to the End of Study Visit (up to 48 months) |
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E.5.2 | Secondary end point(s) |
1. Treatment success after investigational medicinal product (IMP) administration for seizures occurring within the first 12 months 2. Treatment success after IMP administration with no recurrence after 2 hours for seizures occurring within first 12 months 3. Frequency of respiratory TEAEs |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1&2: From start of IMP treatment up to 12 months 3: From Baseline up to the End of Study Visit (up to 48 months) |
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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 | No |
E.8.1.6 | Cross over | Yes |
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 | 5 |
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 | 100 |
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 | No |
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 |
Australia |
China |
Japan |
United States |
France |
Poland |
Bulgaria |
Spain |
Czechia |
Germany |
Italy |
Hungary |
Ukraine |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 20 |