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

NCT ID: NCT02270736

Last Updated: 2021-08-10

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

256 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-02-09

Study Completion Date

2019-05-07

Brief Summary

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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.

Detailed Description

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Conditions

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Chronic Troublesome Sialorrhea Cerebral Palsy Stroke Traumatic Brain Injury Intellectual Disability

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Double-blind MP: Placebo (Age 6 to 17 Years)

Participants will receive placebo via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks. Volumes will be matched to the volumes of NT 201 (incobotulinumtoxinA; Xeomin) injected in the experimental arm.

Group Type EXPERIMENTAL

NT 201 Placebo

Intervention Type DRUG

NT 201 placebo matching injection.

Double-blind, MP: NT 201 (Age 6 to 17 Years)

Participants will receive NT 201 (up to 2.5 Units per kilogram \[U/kg\] body weight) via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks.

Group Type EXPERIMENTAL

NT 201

Intervention Type DRUG

NT 201 injection.

Open-label, MP: NT 201 (Age 2 to 5 Years)

Participants will receive NT 201 (about 1.5-2 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks.

Group Type EXPERIMENTAL

NT 201

Intervention Type DRUG

NT 201 injection.

OLEX: NT 201 (Age 6 to 17 Years)

Participants will receive NT 201 (up to 2.5 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 of second (Visit 6), third (Visit 10), and fourth (Visit 14) injection cycle of the OLEX, followed by an observation period of 16 weeks each (48 weeks in total). This arm will consist of participants who will participate in MP arms "Double-blind, MP: placebo (age 6 to 17 years)" and "Double-blind, MP: NT 201 (age 6 to 17 years)".

Group Type EXPERIMENTAL

NT 201

Intervention Type DRUG

NT 201 injection.

OLEX: NT 201 (Age 2 to 5 Years)

Participants will receive NT 201 (about 1.5-2 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 of second (Visit 6), third (Visit 10), and fourth (Visit 14) injection cycle of the OLEX, followed by an observation period of 16 weeks each (48 weeks in total).

Group Type EXPERIMENTAL

NT 201

Intervention Type DRUG

NT 201 injection.

Interventions

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NT 201 Placebo

NT 201 placebo matching injection.

Intervention Type DRUG

NT 201

NT 201 injection.

Intervention Type DRUG

Other Intervention Names

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IncobotulinumtoxinA Xeomin Botulinum toxin type A (150 kiloDalton), free from complexing proteins

Eligibility Criteria

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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.
Minimum Eligible Age

2 Years

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merz Pharmaceuticals GmbH

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Merz Medical Expert

Role: STUDY_DIRECTOR

Merz Pharmaceuticals GmbH

Locations

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Merz Investigational Site #9950003

K'obulet'i, , Georgia

Site Status

Merz Investigational Site #9950001

Tbilisi, , Georgia

Site Status

Merz Investigational Site #9950002

Tbilisi, , Georgia

Site Status

Merz Investigational Site #0360017

Balassagyarmat, , Hungary

Site Status

Merz Investigational Site #0360013

Budapest, , Hungary

Site Status

Merz Investigational Site # 0360014

Budapest, , Hungary

Site Status

Merz Investigational Site # 0360015

Budapest, , Hungary

Site Status

Merz Investigational Site #0360018

Budapest, , Hungary

Site Status

Merz Investigational Site #0360016

Szombathely, , Hungary

Site Status

Merz Investigational Site #0480092

Bialystok, , Poland

Site Status

Merz Investigational Site #0480090

Gdansk, , Poland

Site Status

Merz Investigational Site #0480076

Katowice, , Poland

Site Status

Merz Investigational Site #0480059

Krakow, , Poland

Site Status

Merz Investigational Site #0480060

Wiązowna, , Poland

Site Status

Merz Investigational Site #0070016

Kazan', , Russia

Site Status

Merz Investigational Site # 0070288

Kemerovo, , Russia

Site Status

Merz Investigational Site #0070290

Khabarovsk, , Russia

Site Status

Merz Investigational # 0070017

Saint Petersburg, , Russia

Site Status

Merz Investigational Site #0070013

Smolensk, , Russia

Site Status

Merz Investigational Site # 070019

Stavropol, , Russia

Site Status

Merz Investigational Site #0070300

Tomsk, , Russia

Site Status

Merz Investigational Site #0070301

Yekaterinburg, , Russia

Site Status

Merz Investigational Site #3810001

Belgrade, , Serbia

Site Status

Merz Investigational Site #3800001

Dnipropetrovsk, , Ukraine

Site Status

Merz Investigational Site #3800012

Ivano-Frankivsk, , Ukraine

Site Status

Merz Investigational Site #3800005

Kharkiv, , Ukraine

Site Status

Merz Investigational Site #3800007

Kharkiv, , Ukraine

Site Status

Merz Investigational Site #3800013

Kherson, , Ukraine

Site Status

Merz Investigational site #3800003

Odesa, , Ukraine

Site Status

Merz Investigational Site #3800009

Ternopil, , Ukraine

Site Status

Merz Investigational Site #3800011

Zaporizhzhya, , Ukraine

Site Status

Countries

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Georgia Hungary Poland Russia Serbia Ukraine

References

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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.

Reference Type RESULT
PMID: 34341153 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36136523 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2013-004532-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MRZ60201_3091_1

Identifier Type: -

Identifier Source: org_study_id

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