E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic troublesome sialorrhea associated with neurological disorders (e.g. cerebral palsy, traumatic brain injury) and/or intellectual disability in children and adolescents |
|
E.1.1.1 | Medical condition in easily understood language |
Chronic troublesome drooling associated with neurological disorders and/ord intellectual disability in children and young persons |
|
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 | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039424 |
E.1.2 | Term | Salivary hypersecretion |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
|
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 |
The objective of this study is to investigate the efficacy and safety of NT 201 compared with placebo for the treatment of chronic troublesome sialorrhea associated with neurological disorders (e.g. cerebral palsy, traumatic brain injury) and/or intellectual disability in children and adolescents naïve to Botulinum neurotoxin treatment and aged 2–17 years. |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Male or female child/adolescent age 2–17 years; Any neurological disorder (e.g. cerebral palsy or traumatic brain injury) and/or intellectual disability associated with chronic troublesome sialorrhea for at least 3 months up to the screening. In subjects with intellectual disability (ID) without neurological disorders, a diagnosis of ID by a specialist, e.g. pediatrician or by a center for developmental medicine is required for inclusion; Severe drooling (modified Teacher´s Drooling Scale [mTDS] ≥ 6; clothing occasionally becomes damp) as rated by the investigator; Parental consent and the subject's oral or written assent as the subject is able to provide |
|
E.4 | Principal exclusion criteria |
" Chronic troublesome sialorrhea not related to neurological disorders and/or intellectual disability; Body weight < 12 kg; Pharmacological treatment for sialorrhea or concomitant medication known to influence sialorrhea strongly (e.g. anticholinergics with exception of locally applied or short acting drugs used under general anesthesia) within 45 days before baseline and during the entire study period; Any previous known or suspected hypersensitivity to Botulinum toxin; Aspiration pneumonia within 6 month before screening; Any previous treatment with Botulinum toxin for any body region during the year before screening or within the screening period; Prior, concomitant or planned surgery or irradiation to head and neck to control sialorrhea (including salivary gland surgery or salivary gland irradiation) within one year before screening or planned for any part of the entire study period; Concurrent diseases, including hematological, hepatic, renal, gastrointestinal, endocrine, pulmonary, musculoskeletal, or psychiatric diseases or conditions, which in the judgment of the investigator would put the subject at risk while in the study, could influence the results of the study, or negatively impact the subject’s ability to participate in the study; Extremely poor dental and/or oral condition that might preclude safe study participation by the judgment of the investigator; Nursing mother or pregnant female subject. "
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
For subjects aged 6–17 years the primary and co-primary variables are: Change in unstimulated salivary flow rate [uSFR] from baseline to Week 4; Global Impression of Change Scale [GICS] at Week 4 representing the functional improvement in drooling since baseline as assessed by the carer/parent(s). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
4 weeks after first injection |
|
E.5.2 | Secondary end point(s) |
For subjects aged 6–17 years: Change in uSFR from baseline to Week 8 and 12;
GICS at Week 8 and 12 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
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 |
Georgia |
Hungary |
Israel |
Poland |
Romania |
Russian Federation |
Serbia |
Turkey |
Ukraine |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |