Clinical trial NCT02270736: Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
Official title: Prospective, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study With an Open-label Extension Period to Investigate the Efficacy and Safety of NT 201 in the Treatment of Children and Adolescents (2-17 Years) With Chronic Troublesome Sialorrhea Associated With Neurological Disorders, and/or Intellectual Disability
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Troublesome Sialorrhea
Cerebral Palsy
Stroke
Traumatic Brain Injury
Intellectual Disability
Lead sponsor: Merz Pharmaceuticals GmbH
Sponsor class: INDUSTRY
First posted: 2014-10-21
Enrollment: 256
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

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.

Primary outcomes:
measure: Change From Baseline in Unstimulated Salivary Flow Rate (uSFR) at Week 4
timeFrame: Baseline and Week 4
measure: Global Impression of Change Scale (GICS) at Week 4 Assessed by the Carer/Parent(s)
timeFrame: Week 4
measure: Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle
timeFrame: Baseline up to Week 64
Secondary outcomes:
measure: Change From Baseline in uSFR at Weeks 8 and 12
timeFrame: Baseline and Weeks 8 and 12
measure: GICS at Weeks 8 and 12
timeFrame: Weeks 8 and 12
measure: Occurrence of Treatment Emergent Adverse Events of Special Interest (AESI) Overall and by Injection Cycle
timeFrame: Baseline up to Week 64
measure: Occurrence of Treatment Emergent Serious Adverse Events (TESAEs) Overall and by Injection Cycle
timeFrame: Baseline up to Week 64
measure: Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and by Injection Cycle
timeFrame: Baseline up to Week 64
measure: Occurrence of TEAEs Leading to Discontinuation Overall and by Injection Cycle
timeFrame: Baseline up to Week 64
Other outcomes:
Locations:
city: Kobuleti
country: Georgia
facility: Merz Investigational Site #9950003
city: Tbilisi
country: Georgia
facility: Merz Investigational Site #9950001
city: Tbilisi
country: Georgia
facility: Merz Investigational Site #9950002
city: Balassagyarmat
country: Hungary
facility: Merz Investigational Site #0360017
city: Budapest
country: Hungary
facility: Merz Investigational Site #0360013
city: Budapest
country: Hungary
facility: Merz Investigational Site # 0360014
city: Budapest
country: Hungary
facility: Merz Investigational Site # 0360015
city: Budapest
country: Hungary
facility: Merz Investigational Site #0360018
city: Szombathely
country: Hungary
facility: Merz Investigational Site #0360016
city: Bialystok
country: Poland
facility: Merz Investigational Site #0480092
city: Gdansk
country: Poland
facility: Merz Investigational Site #0480090
city: Katowice
country: Poland
facility: Merz Investigational Site #0480076
city: Krakow
country: Poland
facility: Merz Investigational Site #0480059
city: Wiazowna
country: Poland
facility: Merz Investigational Site #0480060
city: Kazan
country: Russian Federation
facility: Merz Investigational Site #0070016
city: Kemerovo
country: Russian Federation
facility: Merz Investigational Site # 0070288
city: Khabarovsk
country: Russian Federation
facility: Merz Investigational Site #0070290
city: Saint Petersburg
country: Russian Federation
facility: Merz Investigational # 0070017
city: Smolensk
country: Russian Federation
facility: Merz Investigational Site #0070013
city: Stavropol
country: Russian Federation
facility: Merz Investigational Site # 070019
city: Tomsk
country: Russian Federation
facility: Merz Investigational Site #0070300
city: Yekaterinburg
country: Russian Federation
facility: Merz Investigational Site #0070301
city: Belgrade
country: Serbia
facility: Merz Investigational Site #3810001
city: Dnipropetrovsk
country: Ukraine
facility: Merz Investigational Site #3800001
city: Ivano-Frankivsk
country: Ukraine
facility: Merz Investigational Site #3800012
city: Kharkiv
country: Ukraine
facility: Merz Investigational Site #3800005
city: Kharkiv
country: Ukraine
facility: Merz Investigational Site #3800007
city: Kherson
country: Ukraine
facility: Merz Investigational Site #3800013
city: Odesa
country: Ukraine
facility: Merz Investigational site #3800003
city: Ternopil
country: Ukraine
facility: Merz Investigational Site #3800009
city: Zaporizhzhya
country: Ukraine
facility: Merz Investigational Site #3800011
Study officials:
affiliation: Merz Pharmaceuticals GmbH
name: Merz Medical Expert
role: STUDY_DIRECTOR
References:
citation: Berweck S, Bonikowski M, Kim H, Althaus M, Flatau-Baque B, Mueller D, Banach MD. Placebo-Controlled Clinical Trial of IncobotulinumtoxinA for Sialorrhea in Children: SIPEXI. Neurology. 2021 Oct 4;97(14):e1425-e1436. doi: 10.1212/WNL.0000000000012573.
citation: Berweck S, Banach M, Gaebler-Spira D, Chambers HG, Schroeder AS, Geister TL, Althaus M, Hanschmann A, Vacchelli M, Bonfert MV, Heinen F, Dabrowski E. Safety Profile and Lack of Immunogenicity of IncobotulinumtoxinA in Pediatric Spasticity and Sialorrhea: A Pooled Analysis. Toxins (Basel). 2022 Aug 25;14(9):585. doi: 10.3390/toxins14090585.