E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Obsessive Compulsive Disorders (OCD) Autism Spectrum Disorders (ASD) |
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E.1.1.1 | Medical condition in easily understood language |
OCD: repetitive thoughts/impulses/images and behaviours/mental acts ASD: deficits in social interaction/communication, and restricted, repetitive and stereotyped patterns of behaviour/interests/activ |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063844 |
E.1.2 | Term | Autism spectrum disorder |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029898 |
E.1.2 | Term | Obsessive-compulsive disorder |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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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 |
To investigate clinical effectiveness of memantine in pediatric patients with Obsessive-Compulsive Disorder and Autism Spectrum Disorder with respect to symptoms of compulsivity (assessed as CY-BOCs Total score) and to explore tolerability and safety (based on laboratory measures, adverse events) of memantine in these clinical indications. |
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E.2.2 | Secondary objectives of the trial |
To explore by magnetic resonance imaging the effects of memantine at the level of the structure, function and biochemistry of the brain. To explore additional clinical outcomes, disorder-specific (e.g., core symptoms, response rates, social functioning). To collect blood for genetic analyses and biomarkers and to explore the role of new candidate genes and pathways for compulsivity by linking genes to clinical phenotypes, neurocognitive test performance, and key structural and functional neuroimaging measures of the fronto-striatal circuits. To explore biomarkers / proteomics for compulsivity traits. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Male and female patients Inpatient or outpatient status Aged 6;0 y. (ASD patients) / 8;0 y. (OCD patients) - 17.9 years at initial inclusion IQ ≥ 70 (if an IQ-test was not done within 2 y from Baseline visit, the IQ assessment should be based on Wechsler scales, 4 subtests, cf. 5.1.3) CGI-S score >/= 4 (moderately ill; anchored to respective disorder) at Baseline (BL, visit 3) Ability to speak and comprehend the native language of the country in which the assessments take place Signed informed consent by parents or legal representative Signed informed assent by patients (indicating that the subject is aware of the investigational nature and the core aspects of the study and the study is run in accordance with the ICH GCP guideline E6 (1996)) Female subject must not have a positive beta HCG pregnancy test at screening, and must have a negative urine pregnancy test at baseline (BL), and agree to comply with applicable contraceptive requirements Inclusion criteria for subjects with OCD (GOAT_1): DSM-5 diagnosis of OCD (APA, 2013), according to a systematic interview, e.g., DISC interview, k-SADS Inclusion criteria for subjects with ASD (GOAT_2): DSM-5 diagnosis of ASD (APA, 2013), according to ADI-R interview (shortened version, focusing on criteria for diagnostic decision) |
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E.4 | Principal exclusion criteria |
Mental retardation (IQ < 70) Body weight < 20kg at baseline (BL) Major physical illness of the cardiovascular, endocrine, pulmonary, or the gastrointestinal system Contra-indications for memantine, according to the Summary of Product characteristics (SPC) History of or present clinically relevant somatic acute or chronic disorder that, in the opinion of the investigator, might confound the results of olerability/safety assessment, or prohibit the patients from completing the study, or would not be in the best interest of the patient. Subject has failed to respond, based on investigator judgement, to an earlier adequate course (dose and duration) of the investigational drug therapy, memantine. Subject has a documented allergy, hypersensitivity, or intolerance to memantine. Subject has a lactose intolerance. Subject has a positive urine drug screen result at screening or BL (apart from earlier prescribed medication; retest and negative result at BL needed then) Subject has taken another investigational product or taken part in a clinical study with 30 days prior to screening Subject is female and is pregnant or lactating For those subjects intending to participate in the neuroimaging assessments: All contra indications for MRI assessment, such as the presence of metal objects in or around the body (pacemaker, dental braces)
Patients/parents will not be excluded from the study(ies) in case they do not agree to participate in certain sets of assessments (e.g., neuroimaging, blood sampling for bioanalytical analyses).
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E.5 End points |
E.5.1 | Primary end point(s) |
This research investigates the clinical effectiveness of oral tablet administration of memantine (with respect to oral tablet placebos) on compulsivity scores (Baseline-to-Endpoint change as assessed by CY-BOCS Total score) and explores the tolerability and safety (based on laboratory measures, adverse events) of memantine in these clinical indications in paediatric patients with Obessive-Compulsive Disorder (OCD) or Autism Spectrum Disorder (ASD) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
at: visits 3 - 10 each (BL - wk 12), unscheduled visits, and early discontinuation visit (cf. SOE in study protocol) |
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E.5.2 | Secondary end point(s) |
The endpoints for the secondary objectives are: - Response rates, response defined as >/= 30% reduction vs. BL on primary outcome scale (CY-BOCS Total score for OCD, ASD patients) plus CGI-I score of 1 (very much improved) or 2 (much improved). - Baseline-to-Endpoint changes in ABC Total score (ASD patients) - genotypes of single common and rare variants in candidate genes, and also combined genetic variants in whole genes or neurotransmitter systems / gene pathways; - further lab assessments of various proteins in blood plasma. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
at: visits 3 - 10 each (BL - wk 12), unscheduled visits, and early discontinuation visit (cf. SOE in study protocol); labs for genetics, biomarkers, once at BL (visit 3) |
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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 | 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 | 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 | 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 | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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
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End of trial is defined as the last participant fully assessed during the follow-up wave. |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 31 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 31 |