E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Neurodevelopmental disorders Autism spectrum disorder Attention deficit hyperactivity disorder (ADHD) Learning disorders |
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E.1.1.1 | Medical condition in easily understood language |
developmental disorders autism ADHD learning problems |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
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 |
provide post-trial access to bumetanide treatment for NDD participants |
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E.2.2 | Secondary objectives of the trial |
- to test how bumetanide cohort data relate to the existing RCT data in terms of treatment effectiveness - To further develop EEG biomarker treatment-effect predicotrs - to establish a biobank of blood and skin biopsies for future additional predicitve biomarker development |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- inclusion in BAMBI, BATSCH or BASCET trial - Written informed conset |
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E.4 | Principal exclusion criteria |
1. Inability to comply with the protocol-specified procedures for the duration of the study, including treatment, blood sampling to control diuretic effects; 2. Presence of a severe medical or genetic disorder other than related to ASD, TSC or epilepsy; 3. Serious, unstable illnesses including, gastroenterological, respiratory, cardiovascular (arrhythmias, QT interval lengthening), endocrinologic, immunologic, hematologic disease, dehydration or hypotension, electrolyte disturbances (Na <133 mmol/L, K <3.5 mmol/L or Ca <2.17 mmol/L (<13y) or <2.2 mmol/L (>13y); 4. Renal insufficiency (CKD st2-5; estimated glomerular filtration rate < 90 ml/min/1.73m2), congenital or acquired renal disease with decreased concentration capacity (tubulopathy, diabetes insipidus) and liver insufficiency interfering with excretion or metabolism of bumetanide; 5. Start of behavioral treatment during study; 6. Treatment with psychoactive medications, including antipsychotics and AEDs, except methylphenidate, is allowed if on a stable regime in terms of types and dosage from 2 months prior to the study to the end of the study; 7. Treatment with NSAIDS, aminoglycosides, digitalis, antihypertensive agents, indomethacin, probenecid, acetazolamide, Lithium, other diuretics (e.g., furosemide, hydrochlorothiazide), drugs known to have a nephrotoxic potential; 8. Documented history of hypersensitivity reaction to sulfonamide derivatives; 9. Body weight <30 kg (for reason of dosing).
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E.5 End points |
E.5.1 | Primary end point(s) |
patient reported outcome measures: The parent proxy PROMIS questionnaires that shall be used are: • Physical stress experiences • Psychological stress experience • Sleep disturbances • Sleep-related impairment • Cognitive function • Anxiety • Fatigue • Peer relationships • Life satisfaction • Depressive symptoms
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
weekly for the duration of the study (7-9 months) |
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E.5.2 | Secondary end point(s) |
rsEEg conventional questionnaires (SRS, RBS, SP-NL, ABC) neurocognitive testing |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
rsEEG: monthly Conventional questionnaires: every 3 months neurocognitive testing: every 3 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 | No |
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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
randomized baseline period (A): 2-12 weeks; followed by treatment phase (B): 6 months |
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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 | 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 | 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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |