E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | PT |
E.1.2 | Classification code | 10028713 |
E.1.2 | Term | Narcolepsy |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 assess whether hydralazine in combination with valproate is effective in treating the symptoms of narcolepsy. |
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E.2.2 | Secondary objectives of the trial |
To assess the safety of treating NT1 patients with hydralazine in combination with valproate. To assess whether the efficacy of hydralazine in combination with valproate is reflected in an increased concentration of hypocretin-1 in the CSF. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Fulfilling the ICSD3 criteria for NT1, including a hypocretin-1 level in the CSF < 110 pg/ml. - Recent symptoms of narcolepsy (< 5 years). - Baseline Epworth Sleepiness Scale (ESS) ≥ 14. - > 7 cataplexy attacks per week (complete or partial) at baseline as assessed by a cataplexy diary. - Regular schedule for nocturnal sleep and time in bed > 6 hrs as assessed by actigraphy and sleep diary. - BMI 18-35 kg/m2. - For females: use of a medically acceptable method of contraception for at least 2 months prior to the first dose of study drug and consent to continue the practice throughout the entire study and for 30 days after the study is completed. No pregnancy planned for one year after participation. - Willing and able to comply with the study design schedule and all other requirements. - Willing and able to provide written informed consent. |
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E.4 | Principal exclusion criteria |
- Use of any psychotropic medication during the last 6 weeks before inclusion, with exception for stimulants: use of stimulants during the last week before inclusion. - Pharmacological treatment for hypertension or epilepsy. - Female subjects who are pregnant (as assessed by pregnancy test at baseline), nursing or lactating. - Occupation requiring nighttime shift work or variable shift work. - Any other severe clinically relevant medical, behavioural, or psychiatric disorder, particularly past or present condition of heart failure from aortic stenosis and postural hypotension as diagnosed by a physician. - Any contraindication against using either hydralazine or valproate. - Significant laboratory abnormality as assessed during baseline. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Weekly cataplexy rate (complete/partial) as assessed in a diary before and after treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Before and after administration of study medication. |
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E.5.2 | Secondary end point(s) |
- Change in daytime sleepiness as assessed by the Epworth Sleepiness Scale (ESS).- Improvement of fragmentation index, sleep efficiency and REM latency on the polysomnography (PSG). - Improvement of mean sleep latency (> 8 min) and/or sleep-onset REM periods (SOREMPs; < 2) during the Multiple Sleep Latency Test (MSLT); - Adverse events (AEs); - Changes in vital signs upon treatment; - Increase in hypocretin-1 levels in the CSF measured by radioimmunoassay (only assessed if substantial improvement on the primary endpoints after 6 weeks of treatment, defined as ESS <12 or ESS > 4 points decreased and/or weekly cataplexy rate > 75% decreased). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Before and after administration of study medication. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
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 | 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 | No |
E.8.1.1 | Randomised | No |
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 | No |
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 | No |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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 |
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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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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 | 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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |