E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Children and adolescents aged 2 to 18 years, corresponding to F84.0 (Childhood Autism) or F84.5 (Asperger's Syndrome) according to the International Statistical Classification of Diseases and Related Health Problems, tenth revision (ICD-10) and with a Childhood Autism Rating Scale (CARS) score > 34. |
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E.1.1.1 | Medical condition in easily understood language |
Autism and/or Asperger's Syndrom |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Behaviours [F01] |
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 |
To determine the optimal dose strength for the pivotal Phase III study; |
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E.2.2 | Secondary objectives of the trial |
•To evaluate the pharmacokinetics (PK) of Bumetanide in children and adolescents with ASD;
•To confirm the efficacy of Bumetanide in the treatment of children and adolescents with autistic spectrum Disorder (ASD).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Male or female patients aged 2 to 18 years, inclusive;
2.F84.0 (Childhood Autism) or F84.5 (Asperger's Syndrome) scores according to the International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10);
3.Patients meeting criteria for autism on Autism Diagnosis Interview-Revised (ADI-R).
4.CARS score > 34 points;
5.The patient is able to comply with the protocol for the duration of the study, including treatment, blood sampling and scheduled follow-up visits and examinations;
6.The patient's parent/guardian has given written informed consent, prior to any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
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E.4 | Principal exclusion criteria |
1.Serious, unstable illnesses including, gastroenterologic, respiratory, cardiovascular (QT interval lengthening), endocrinologic, immunologic, or hematologic disease;
2.Renal or hepatic dysfunction that would interfere with excretion or metabolism of Bumetanide;
3.Patients with any specific neurological disorders like seizures, microcephaly;
4.Patients taking psychoactive medications except melatonin;
5.Documented history of hypersensitivity reaction to sulfonamide derivatives.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in CARS from baseline (Day 1) to Day 90.
The treatment groups will be compared using a non-parametric test as specified in the Statistical Analysis Plan.
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E.5.2 | Secondary end point(s) |
By way of further confirmatory measures of efficacy, the following endpoints will be analyzed:
•CGI-I scale;
•The Vineland Adaptive Behavior Scales (Vineland-II) (personal and social skills);
•The Social Responsiveness Scale (SRS) (focuses on the child’s reciprocal social interactions);
•QOL
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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 | 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 | Yes |
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) | 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 | 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
| 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 | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |