E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
- Obsessive-compulsive disorder
- Autistic Diorder, Aspergers' Disorder, PDD NOS |
|
E.1.1.1 | Medical condition in easily understood language |
patients with obsessive-compulsive disorder and 'autistic disorders' exhibiting compulsive symptoms will be studied |
|
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 |
Primary objectives are:
1) To investigate clinical effectiveness of the glutamatergic compound memantine in paediatric patients with:
- Obessive-Compulsive Disorder (OCD) GOAT-1
- Autism Spectrum Disorder (ASD) GOAT-2
with respect to symptoms of
- ‘compulsivity’ (assessed as CY-BOCs Total score) and/or
2) To explore tolerability and safety (based on laboratory measures, adverse events) of the compound(s) in these clinical indications.
|
|
E.2.2 | Secondary objectives of the trial |
Secondary objective(s) are:
3) To explore the effects of glutamategic interventions at the level of the structure, function and biochemistry of the fronto-striatal circuits (MRI, MRS),
in subgroups (disorders, age range, meeting inclusion/exclusion criteria of the COMPULS study
protocol from the TACTICS project).
4) To collect: blood for genetic analyses and biomarkers.
5) To explore: additional clinical outcomes, disorder-specific (e.g., core symptoms, response rates,
social functioning).
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
General inclusion criteria for both patient groups (GOAT 1 – 2)
• 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 (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
Inclusion criteria for subjects with ASD (GOAT-2)
• DSM-5 diagnosis of ASD (APA, 2000), according to ADI-R interview (shortened version, focusing on criteria for diagnostic decision)
|
|
E.4 | Principal exclusion criteria |
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 bioanalytic analyses).
General exclusion criteria for all subject groups
• Mental retardation (IQ < 70)
• Body weight < 20kg at baseline (BL)
• Major physical illness of the cardiovascular, endocrine, pulmonal, 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 tolerability/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 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)
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The endpoints for the primary objective-1 are:
outcome measures (Baseline-to-Endpoint change) of
- compulsivity (CY-BOCS Total score (all patients)),
The endpoints for the primary objective-2 are:
- adverse event (AE) rates, derived from spontaneous reporting and a structured AE instrument,
the (shortened/modified) Paediatric Adverse Event Rating Scale (PAERS).
|
|
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) |
|
E.5.2 | Secondary end point(s) |
The endpoints for the secondary objectives are:
- Additional clinical outcomes, e.g. :
- 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.
|
|
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) |
|
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 | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
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 | 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
|
LVLS (in general)
Possibility to stop the study early in case of severe safety/tolerability issues and/or (new) ethical concerns,
after consultation with TACTICS consortium's steering committee and the independent scientivic Advisory Board/Data Monitoring Board. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |